Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Sci Signal. Author manuscript; available in PMC 2011 May 2.
Published in final edited form as:
PMCID: PMC3085344

Basal Release of ATP: An Autocrine-Paracrine Mechanism for Cell Regulation


Cells release adenosine triphosphate (ATP), which activates plasma membrane–localized P2X and P2Y receptors and thereby modulates cellular function in an autocrine or paracrine manner. Release of ATP and the subsequent activation of P2 receptors help establish the basal level of activation (sometimes termed “the set point”) for signal transduction pathways and regulate a wide array of responses that include tissue blood flow, ion transport, cell volume regulation, neuronal signaling, and host-pathogen interactions. Basal release and autocrine or paracrine responses to ATP are multifunctional and evolutionarily conserved, and they provide an economical means for the modulation of cell, tissue, and organismal biology.


The regulation of cellular function by extracellular hormones, neurotransmitters, nutrients, growth factors, and other factors known as “first messengers” commonly alters the intracellular concentrations of second messengers and, in turn, those of “downstream” signaling components [sometimes termed “third messengers” (1, 2)]. Some cells are also regulated by “inside-out” signaling, whereby cytoplasmic events are transmitted to external ligand-binding domains or receptors (3-5) through bidirectional communication between cells that have ligands and complementary receptors on their plasma membranes (6). The release of intracellular adenosine triphosphate (ATP) and perturbation of function by released ATP is another type of signaling but is less commonly recognized. Such signaling can occur in the same cell that releases ATP (autocrine signaling), on neighboring cells (paracrine signaling), or both.

Evidence for a cellular response to ATP was first noted in the 1920s (7), but even so, the idea that cells could release and respond to released ATP, proposed more than 30 years ago (8), was met with much skepticism (9). Virtually every type of eukaryotic cell releases ATP and has plasma membrane–localized nucleotide-activated (P2) receptors, which implicate ATP and other nucleotides as ubiquitous extracellular modulators of cell function (10, 11). Less well appreciated is the release of ATP under basal conditions and the resulting induction of autocrine and paracrine responses. Basal release of ATP can be increased by minimal perturbation of cells through physical or chemical stimuli. Our focus here is ATP, but cells release other nucleotides [for example, uridine triphosphate (UTP) and related molecules such as uridine diphosphate (UDP) sugars] that have actions akin to those of ATP (12, 13).

Cellular Release of ATP

Multiple mechanisms mediate the release of intracellular ATP in response to mechanical stimulation or extracellular biochemical cues (14). Mechanical stimulation can occur by osmotic swelling or shrinking of cells (15-34), physical perturbation [for example, flow or stretching forces (35-44)], host-pathogen interactions (45-47), or even by changing the extracellular media (48-50). Merely tilting a plate of cells or adding media can induce the release of ATP at sufficient concentrations to trigger cellular signaling pathways (51). Such results imply that numerous—perhaps most—experiments with cultured or isolated cells in which investigators wash cells, replace the extracellular media, or add drugs or other chemicals can promote the release of ATP, which, in turn, alters cellular function by itself or through its metabolic products, such as adenosine (52). Such actions of released ATP are rarely considered in experiments with cultured or isolated cells. Mechanical and chemical stimulation also promotes the release of ATP in vivo from skeletal muscle (53), heart (54), and erythrocytes (55) and in the nervous system, including the trigeminal and dorsal root ganglia (56, 57), ventral medulla (58), cochlea (59), and glia (60).

Cellular release of ATP can be detected by many methods, most commonly by luciferase-catalyzed, ATP-dependent generation of light by the substrate luciferin (61). Use of this method is problematic with cells that have substantial amounts of proteases, ATP hydrolytic activity (for example, in granulocytes), or both, and thus alternative assays with different detectors of ATP have been developed (62, 63). Imamura et al. described the use of a fluorescence resonance energy transfer (FRET)–based indicator (the ε-subunit of the bacterial FoF1-ATP synthase together with cyan and yellow fluorescent proteins) as another approach to detect extracellular ATP (64).

Release of ATP by cells occurs through multiple mechanisms. Early studies suggested that the cystic fibrosis transmembrane regulator (CFTR) was responsible for this release; however, later work indicated that it was more likely that CFTR regulates, rather than mediates, the release of ATP (49, 65, 66). Multiple types of membrane channels mediate ATP release, including connexin and pannexin hemichannels (67, 68), maxi-anion channels (69, 70), volume-regulated anion channels (71, 72), and the P2X7 receptor (73). Mechanisms for the release of ATP have been recently reviewed (9, 74-76). In addition to release through channels, nonexcitatory cells can release ATP by exocytotic mechanisms in response to biochemical and mechanical stimuli, much as neurons do on depolarization (77-79).

Receptor Targets of Extracellular ATP

Extracellular ATP exerts a wide range of cellular effects by activating plasma membrane–localized receptors that belong to one of two classes: heterotrimeric guanine nucleotide–binding protein (G protein)–coupled P2Y receptors and ion channel P2X receptors. Mammalian cells have eight P2Y receptor subtypes, two of which are preferentially activated by ATP (P2Y2 and P2Y11), although ATP or ATP-derived products, such as adenosine diphosphate (ADP), interact with other P2Y receptors (10) (Table 1). P2Y receptors regulate signal transduction through the heterotrimeric G proteins of the Gi, Gq/11, and Gs families (10).

Table 1
Isoforms of P2Y and P2X receptors and their primary endogenous agonists

By contrast with the selectivity of P2Y receptors for different nucleotides, ATP activates all of the seven mammalian P2X receptors (11). P2X receptors have three subunits that are assembled in homomeric or heteromeric complexes (80, 81). One P2X receptor, P2X4 from zebrafish, has been crystallized and has three intersubunit binding sites for ATP; occupancy by ATP appears to promote subunit rearrangement and opens the ion channel (82). P2Y receptors have not been crystallized, but the use of other techniques has led to predictions regarding their three-dimensional structures (83).

In addition to its ability to activate P2X and P2Y receptors, extracellular ATP is hydrolyzed by membrane ecto-nucleotideases, including adenosine triphosphatases (ATPases) (84, 85). Ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) hydrolyze nucleotide diphosphates and triphosphates to generate nucleotide monophosphates, and they are the largest family of ectonucleotidases, consisting of E-NTPDase1 to 8, including E-NTPDase1 (CD39), E-NTPDase2 (CD39L1), E-NTPDase3 (CD39L3), E-NTPDase5 (CD39L4), and ENTPDase6 (CD39L2) (86). There are five members of the family of ectonucleotide pyrophosphatase and phosphodiesterases (E-NPPs), the second largest ectonucleotidase family, which hydrolyze nucleotide triphosphates to generate nucleotide monophosphates and extracellular inorganic pyrophosphate (87) and can convert cyclic adenosine monophosphate (cAMP) to adenosine (88). Alkaline phosphatases, another family of ecto-ATPases, consist of four isoforms (84). Ecto-5′-nucleotidase (CD73) catalyzes the conversion of AMP to the nucleoside adenosine (89). Adenosine, the f inal product of ecto-ATPase action, activates P1 (also known as A1 to A3) receptors, which are G protein–coupled receptors that couple to Gs or Gi proteins (90). The function of cells that release ATP can be altered by the activation of P2 receptors [or P1 receptors if adenosine is generated (Fig. 1)]; P1 or P2Y receptors and ecto-ATPases heterooligomerize and may form membrane networks (91). Stimulation of the receptors by agonists changes membrane potential, the cellular content of ions and second messengers, or both and, in turn, alters the abundance and activity of effector molecules and components regulated by such signaling events.

Fig. 1
Autocrine and paracrine actions of extracellular ATP

Autocrine and Paracrine Actions of Extracellular ATP

The release of ATP alters cell physiology in multiple ways. Among these is basal release of ATP, which acts through autocrine or paracrine stimulation of P2 receptors (and following its hydrolysis to adenosine, of P1 receptors) to contribute to the set point of second-messenger systems (52). Such set points, which reflect the activation of signaling pathways, help define the dynamic range of responses: ATP affects the abundance of intracellular Ca2+ and cAMP and the activation of protein kinases, including cAMP-dependent protein kinase (PKA), protein kinase C (PKC), and Ca2+- and calmodulin-dependent protein kinases. The contribution of released ATP and its metabolites to signaling events and cell function are rarely considered in studies of signal transduction or downstream cellular responses of other ligands. Treatment of cells with adenosine 5′-triphosphatase (an apyrase), which rapidly hydrolyzes ATP, is a means of defining such a contribution. Apyrase is commonly used in studies of platelet activation and aggregation in order to block the secondary wave of aggregation that is mediated by ADP released from platelet storage granules. Use of apyrase has shown that endogenously released ATP contributes to ambient levels of activation of signal transduction pathways. There are many other examples of cell types in which apyrase or other approaches have been used to identify a role for ATP release in cell regulation (Table 2).

Table 2
Autocrine and paracrine activities of released ATP

Released ATP modulates cellular responses to neurotransmitters and hormones. ATP receptors induce actions that may be additive or antagonistic to those of other agonists; in addition, released ATP causes heterologous desensitization of receptors and thereby alters responses to other types of agonists (92, 93). Released ATP also influences cellular function by modulating the abundance of intracellular Ca2+, including by the generation and propagation through gap junctions of Ca2+ waves between cells (21, 36, 37, 43, 44). Heterogeneity in the abundance of P2Y2 receptors and their activation by extracellular nucleotides help determine variations in Ca2+ signaling among cells in a population (94). Relatively few studies of mechanisms that regulate Ca2+ abundance and Ca2+-dependent processes have also assessed the contribution of ATP release to these processes when stimuli are used that elicit such release. Below, we highlight examples of cellular regulation that occur by release of and response to endogenous ATP, which include such processes as tissue blood flow, control of cell volume, growth and metastatic potential of malignant cells, neuronal activity, neural development, and response to pathogens.

Regulation of Tissue Blood Flow

Constituitive release of ATP from the luminal membrane of vascular endothelial cells modulates vascular tone through P2X and P2Y receptors on those cells (18, 87, 95). ATP is also released as a cotransmitter with norepinephrine from perivascular sympathetic nerves onto vascular smooth muscle cells, where it promotes vasoconstriction by activating P2X1 receptors (96). In addition to basal release of ATP, increased release from endothelial cells occurs in response to shear stress, hypoxia, or ischemia and promotes P2 receptor–mediated vasodilation (97-100). P2 receptor–regulated signaling cascades release vasodilators that include nitric oxide (101, 102), prostaglandins (103, 104), and endothelium-derived hyperpolarizing factor (105-107).

Cells exposed to the luminal membrane of the vascular endothelium contribute to the regulation of vascular tone and blood flow by releasing ATP that acts in a paracrine manner (Fig. 2). An important role for erythrocytes as oxygen sensors that release ATP under hypoxic conditions to modulate vascular tone was outlined in a series of studies by Bergfield et al., Ellsworth et al., and Dietrich et al. (108-110). During oxygen deprivation, cerebral and other arterioles release ATP, which promotes vasodilation and increases blood flow (110). This vasodilation is regulated by P2Y13 receptors, which are activated by ADP and inhibit the release of ATP from erythrocytes, thus creating a feedback loop for the control of blood flow (111). Low basal concentrations of ATP and ADP are found outside of platelets and are regulated by NTPDase-1 (112, 113). On activation, platelets release ADP from storage granules, thereby altering blood flow and platelet aggregation. Clopidogrel and related compounds are drugs used in the treatment of thromboembolic disease that target platelet P2Y12 receptors for which ADP is the physiological agonist (114). ATP released by leukocytes influences the function of other blood cells and of vascular endothelial cells (47, 115-121); ATP released in the kidney regulates blood flow and renal function (122).

Fig. 2
Control of blood flow by autocrine and paracrine ATP signaling

Ion Transport and Control of Cell Volume

Extracellular ATP has an important impact on ion transport in numerous cell types (Table 2), in particular, in response to changes in their osmotic environment (“osmotic stress”) (123). To maintain their volume under such conditions, cells increase ionic secretion by a process termed regulatory volume decrease (RVD) (124). Osmotic stress promotes the release of ATP, which, through its activation of P2 receptors, contributes to RVD by triggering a Ca2+-dependent increase in the secretion of ions (27-30, 32, 33, 125). Inhibition of ATP signaling (by ATP scavengers, such as apyrase, or P2 receptor blockers, such as suramin) slows volume recovery and blocks Cl currents (27, 30). Increasing ATP conductance, by increasing the abundance of multidrug resistance (Mdr) proteins in hepatic cells, results in a more rapid recovery after hypotonic exposure (28). This release of ATP is dependent on the volume of the cell; increasing hypoosmotic pressure increases the release of ATP (30). Inhibition of Ca2+ signaling inhibits membrane currents, but swelling-induced increases in the concentration of Ca2+ are unaffected by apyrase or suramin, which suggests the existence of P2 receptor–independent Ca2+ signaling and Ca2+-independent purinergic signaling pathways (126).

Extracellular ATP contributes to RVD in other cell types, although the precise mechanisms by which cell volume is regulated vary. In erythrocytes, P2 receptors potentiate RVD by stimulating K+ efflux in a Ca2+-dependent manner (127, 128). In African green monkey kidney (Vero) cells, ATP activates K+ currents by increasing the concentration of cytososolic Ca2+ and activating Ca2+-dependent K+ channels (129, 130). In human intestinal 407 cells, ATP-induced mobilization of Ca2+ stimulates K+ currents and mediates the hypotonicity-promoted activation of extracellular signal–regulated kinase 1 (ERK1) and ERK2 (131, 132). In rat biliary cells, release of ATP from the apical and basolateral membranes facilitates RVD in response to hypotonic stress (31). Antibody-tethered luciferase molecules, which facilitate the analysis of local concentrations of ATP, have been used in experiments with human bronchial epithelial cells to show that upon hypotonic challenge, the concentration of ATP just outside the cell membrane increases 100- to 1000-fold compared with that under basal (isotonic) conditions and approaches a concentration of 1 μM (133). Loss of CFTR and CFTR-mediated autocrine ATP signaling are potentially responsible for defective regulation of cell volume and the altered function of airway epithelia in cystic fibrosis, in particular, as related to the airway surface fluid layer (33).

Extracellular ATP signaling regulates excitatory amino acid (EAA) release from astrocytes, in particular, from osmotically swollen astrocytes, by modulating volume-regulated anion channels (134, 135). Astrocytes contain P2Y1 receptors, activation of which increases the concentration of intracellular Ca2+ and causes the release of glutamate, likely through the actions of PKC-α and PKC-βI (136, 137). Ambient concentrations of extracellular ATP modulate Na+ transport in renal epithelial cells, including in collecting duct cells through the activation of P2Y2 (138). Activation of basolateral P2Y2 receptors inhibits arginine vasopressin–induced water transport in the medullary collecting duct (139). Mice deficient in P2Y2 receptors have salt-resistant hypertension, alterations in renal epithelial cell regulation of ions, and perturbation of renal concentrating mechanisms (140-142).

Propagation and Metastatic Potential of Cancer Cells

Autocrine and paracrine ATP signaling contribute to tumorigenesis, in part because extracellular ATP serves as a growth factor (143). The basal rate of ATP release is increased and the extent of hydrolysis of extracellular nucleotides is decreased in neoplastic tissues and cells; such changes, through P2 receptor signaling, potentially increase cell proliferation (144, 145). Extracellular ATP may contribute to tumorigenesis in multiple ways. Concentrations of extracellular ATP that are 10 μM and higher enhance the death of cervical (146), gastrointestinal (23, 147), and prostate cancer cells (148) by a mechanism that may involve the activation of P2X7; resistance to cell death may contribute to the enhanced proliferation of such cells. Certain cancer cells, including B lymphocytic leukemia (149) and carcinomas of the prostate and thyroid (150, 151), have an increased abundance of P2X7 receptors, which are potential therapeutic targets for cell killing (151). Release of ATP by cancer cells exerts paracrine effects and influences tumor biology: ATP released from fibrosarcoma cells increases the intracellular concentration of Ca2+ in endothelial cells and may contribute to invasion and metastasis (152). The effects described above with regard to the impact of released ATP on tissue blood flow also may contribute to the growth and microenvironment of tumors.

Neuronal Signaling and Neural Development

ATP is an excitatory cotransmitter in neuronal cells (67). Release of ATP from neuron-like PC12 cells modulates cell function (153). The release of ATP and its actions and those of its hydrolytic products have roles in other neuronal and neuroendocrine cells, for example, as neurotransmitters and gliotransmitters in the retina, olfactory epithelium, taste buds, and cochlea; nucleotide receptor signaling thus contributes to sensory transduction and to the function of other types of neurons (154, 155).

Extracellular ATP signaling regulates neuronal cell proliferation and differentiation. PC12 cells and dorsal root ganglion neurons release ATP, which, through the activation of P2Y2 receptors, is a coactivator of neurotrophin-TrkA–dependent neuronal differentiation (156, 157). Such results identify ATP as a morphogen and P2Y2 as a morphogen receptor during neural development, perhaps through mechanisms that include P2Y2-TrkA crosstalk and activation of Src family kinases (156, 157). ATP promotes cell proliferation in certain neurons [for example, in the chick neural retina at early embryonic stages (158)]. P2Y receptor antagonists inhibit proliferation and promote the differentiation of neural progenitor cells through P2Y1 receptors (159, 160). Multiple P2 receptors are likely involved in neuronal differentiation and proliferation, as there is evidence that nerve growth factor–promoted differentiation of PC12 cells increases the abundance of P2X receptors (161).

Host-Pathogen Interactions

Autocrine and paracrine ATP signaling can contribute to cellular response to pathogens, such as the production and release of inflammatory mediators, including cytokines. In some cases, agents that contribute to pathogenicity increase the extent of basal release of ATP. For example, treatment of microglia with the bacterially derived endotoxin lipopolysaccharide (LPS) releases ATP and promotes the production of interleukin 1β (IL-1β) and IL-10 (162-164). LPS-stimulated release of ATP also promotes the release of IL-1α from endothelial cells and that of IL-6 from fibroblasts (165, 166). Microbial components and uric acid (a “danger signal” released from dying cells) promote the secretion of IL-1β and IL-18 from monocytes by stimulating the release of ATP (47), although uric acid can activate the IL-1–processing inflammasome in the absence of P2X7 receptor activity (167). Released ATP is thus a proinflammatory signal during the acute inflammation that occurs in damaged or infected tissues.

ATP signaling in response to pathogens stimulates apoptosis through activation of P2X7 receptors, perhaps as an attempt to fight infection (162, 166). Bacterially derived peptides such as the N-formyl peptide fMet-Leu-Phe [(fMLP) in humans and certain other animals] and W-peptide (Trp-Lys-Tyr-Met-Val-d-Met-NH2 in mice) stimulate the relase of ATP from neutrophils and stimulate neutrophil migration and phagocytosis (116). In an analogous manner, salivary histatin 5 (Hst 5), a human antimicrobial peptide, stimulates the release of ATP from the fungus Candida albicans and promotes cell death through the activation of a P2X7-like receptor (168, 169).

The survival of some pathogens is enhanced by their modulation of nucleotide release and signaling by host cells. Intracellular survival of Mycobacterium avium subspecies paratuberculosis depends on the release of ATP; treatment of infected monocytes with the ATP scavenger apyrase decreases the number of intracellular bacilli (170). Respiratory syncytial virus blocks the clearance of fluid by the bronchoalveolar epithelium through a mechanism that involves nucleotide release and activation of host P2Y receptors (171). Leishmania amazonensis releases nucleoside diphosphate kinase, which decreases the concentration of extracellular ATP and prevents ATP-induced cytolysis of macrophages and thus preserves the integrity of host cells to the benefit of the parasite (172). OppA, the ecto-ATPase of Mycoplasma hominis, induces ATP release and death of infected HeLa cells, which may promote dissemination of the microorganism (173). Of note, the saliva of biting insects such as Aedes aegypti (the mosquito host for yellow fever), Culicoides variipennis, and Phlebotomus papatasi contain apyrases that hydrolyze ATP (174-176). Thus, release of extracellular ATP influences interactions between pathogens and their target cells, as well as affecting the innate immune response. Other data implicate a role for the relase of ATP and ATP-mediated responses in lymphocyte functions that contribute to adaptive, as well as to innate, immunity (47, 118, 177). Autocrine and paracrine ATP signaling have other functional roles, including regulation of the secretion and function of endocrines (168, 178-183), the functions of muscles and tendons (48, 184, 185), the formation and resorption of bone (186, 187), and the proliferation of stem cells (41, 42) (Table 2). The diverse array of cellular responses to extracellular ATP illustrates its importance as a signaling molecule that regulates many biologic activities.


In addition to the essential role of ATP as the primary unit of energy in cells, its release and autocrine and paracrine effects influence a large number of cell types and responses. This raises an important question: Why would a cell release life-sustaining energy stores in order to generate a signaling molecule? In most cells, the intracellular concentration of ATP is ~1 mM (188); concentrations of extracellular ATP in the near-membrane environment are in the low micromolar range, but such concentrations are sufficient to trigger functional changes (116, 133, 189, 190). The ability of low concentrations of ATP (relative to those found intracellularly) to induce responses and the favorable concentration gradient, potency, and efficacy of ATP as a signaling molecule make it a highly efficient means for autocrine and paracrine regulation of cells. Adenosine, which is generated by ATPase-catalyzed hydrolysis, enhances the scope of action of extracellular ATP. Some cells produce extracellular enzymes that regenerate ATP and help potentiate responses activated by the released nucleotide (191). The diverse array of receptors for ATP and adenosine and the range of ecto-ATPases and kinases that regulate extracellular concentrations create a highly economical, versatile, and tightly regulated system to facilitate cellular regulation by extracellular ATP derived from internal pools of nucleotides.

ATP signaling may have evolved as a danger signal in response to the release of ATP by damaged cells. Extracellular ATP is a chemorepellent in two unicellular eukaryotes, Tetrahymena thermophila and Paramecium tetraurelia, which migrate away from sources of the nucleotide (192, 193). ATP depolarizes these cells, modulates changes in the concentration of intracellular Ca2+, and directs the cells to reverse their direction of movement. In P. tetraurelia, the ATP receptor pharmacologically resembles mammalian P2X1 receptors (193). P2X-like receptors have been characterized in Schistosoma mansoni (194) and in Dictyostelium discoideum, in which they function as osmoregulators (195).

The evolutionary origin of ATP signaling may have a parallel with that of the cAMP signaling system, which directs D. discoideum migration in conditions of starvation; when released from cells, cAMP acts as a chemoattractant and influences the migration of neighboring cells (196). Analogously, release of ATP by murine and human neutrophils directs cell migration in an autocrine manner (116), and its release by apoptotic cells has been implicated as a paracrine “find-me” signal to promote phagocytic clearance (197) Perhaps cAMP and ATP are used by different organisms as alternative nucleotides for autocrine and paracrine signaling, a notion consistent with the evolutionary expression of P2Y receptors (198) and with the proposal that cAMP is part of a metabolic code in prokaryotes and eukaryotes (2). Of note, cells use ATP and UTP (12, 13), a purine and pyrimidine, not only for the synthesis of DNA and RNA but also as extracellular signaling molecules.

Released ATP thus plays a large number of autocrine and paracrine roles in the regulation of cell physiology. Many cell types release functionally relevant concentrations of ATP in response to stimuli that minimally perturb the cells. Extracellular ATP signaling helps establish the set point of signaling pathways and affects the responses of cells to other stimuli. To what extent do the cellular release of ATP and the signaling pathways regulated by ATP and its metabolic products contribute to responses previously (and perhaps, in part, mistakenly) attributed to other molecules? Given the conserved nature of ATP release and signaling pathways, we believe that the role of released ATP in signal transduction, physiology, and pathophysiology has yet to be fully discovered.


Work in the authors’ laboratory on this topic is supported by grants from the National Institutes of Health, the Ellison Medical Foundation, and the Lymphoma and Leukemia Society. R.C. is currently supported by a postdoctoral fellowship from the British Pharmacology Society.

References and Notes

1. Wollenberger A, Will H, Krause EG, Wollenberger A, Will H, Krause EG. Adenosine 3′,5′-monophosphate, the myocardial cell membrane, and calcium. Recent Adv. Stud. Cardiac Struct. Metab. 1975;5:81–93. [PubMed]
2. Tomkins GM. The metabolic code. Science. 1975;189:760–763. [PubMed]
3. Ménasché G, Kliche S, Bezman N, Schraven B. Regulation of T-cell antigen receptor-mediated inside-out signaling by cytosolic adapter proteins and Rap1 effector molecules. Immunol. Rev. 2007;218:82–91. [PubMed]
4. Coller BS, Shattil SJ. The GPIIb/IIIa (integrin alphaIIbbeta3) odyssey: A technology-driven saga of a receptor with twists, turns, and even a bend. Blood. 2008;112:3011–3025. [PMC free article] [PubMed]
5. Takabe K, Paugh SW, Milstien S, Spiegel S. “Inside-out” signaling of sphingosine-1-phosphate: Therapeutic targets. Pharmacol. Rev. 2008;60:181–195. [PMC free article] [PubMed]
6. Pasquale EB. Eph-ephrin bidirectional signaling in physiology and disease. Cell. 2008;133:38–52. [PubMed]
7. Drury AN, Szent-Györgyi A. The physiological activity of adenine compounds with especial reference to their action upon the mammalian heart. J. Physiol. 1929;68:213–237. [PMC free article] [PubMed]
8. Burnstock G. Historical review: ATP as a neurotransmitter. Trends Pharmacol. Sci. 2006;27:166–176. [PubMed]
9. Burnstock G. Unresolved issues and controversies in purinergic signalling. J. Physiol. 2008;586:3307–3312. [PMC free article] [PubMed]
10. Abbracchio MP, Burnstock G, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, Knight GE, Fumagalli M, Gachet C, Jacobson KA, Weisman GA. International Union of Pharmacology LVIII: Update on the P2Y G protein-coupled nucleotide receptors: From molecular mechanisms and pathophysiology to therapy. Pharmacol. Rev. 2006;58:281–341. [PMC free article] [PubMed]
11. Khakh BS, Burnstock G, Kennedy C, King BF, North RA, Séguéla P, Voigt M, Humphrey PP. International Union of Pharmacology XXIV: Current status of the nomenclature and properties of P2X receptors and their subunits. Pharmacol. Rev. 2001;53:107–118. [PubMed]
12. Lazarowski ER, Shea DA, Boucher RC, Harden TK. Release of cellular UDP-glucose as a potential extracellular signaling molecule. Mol. Pharmacol. 2003;63:1190–1197. [PubMed]
13. Lazarowski E. Regulated release of nucleotides and UDP sugars from astrocytoma cells; Novartis Found. Symp.; 2006; pp. 73–84. discussion 84–90, 107–112, 275–281. [PubMed]
14. Schwiebert EM, Zsembery A. Extracellular ATP as a signaling molecule for epithelial cells. Biochim. Biophys. Acta. 2003;1615:7–32. [PubMed]
15. Mongin AA, Kimelberg HK. ATP potently modulates anion channel-mediated excitatory amino acid release from cultured astrocytes. Am. J. Physiol. Cell Physiol. 2002;283:C569–C578. [PubMed]
16. Darby M, Kuzmiski JB, Panenka W, Feighan D, MacVicar BA. ATP released from astrocytes during swelling activates chloride channels. J. Neurophysiol. 2003;89:1870–1877. [PubMed]
17. Hisadome K, Koyama T, Kimura C, Droogmans G, Ito Y, Oike M. Volume-regulated anion channels serve as an auto/paracrine nucleotide release pathway in aortic endothelial cells. J. Gen. Physiol. 2002;119:511–520. [PMC free article] [PubMed]
18. Schwiebert LM, Rice WC, Kudlow BA, Taylor AL, Schwiebert EM. Extracellular ATP signaling and P2X nucleotide receptors in monolayers of primary human vascular endothelial cells. Am. J. Physiol. Cell Physiol. 2002;282:C289–C301. [PubMed]
19. Hong D, Barbee KA, Buerk DG, Jaron D. Heterogeneous cytoplasmic calcium response in microvascular endothelial cells; Conf. Proc. IEEE Eng. Med. Biol. Soc.; 2005.pp. 7493–7496. [PubMed]
20. Gomes P, Srinivas SP, Vereecke J, Himpens B. ATP-dependent paracrine intercellular communication in cultured bovine corneal endothelial cells. Invest. Ophthalmol. Vis. Sci. 2005;46:104–113. [PubMed]
21. Henriksen Z, Hiken JF, Steinberg TH, Jørgensen NR. The predominant mechanism of intercellular calcium wave propagation changes during long-term culture of human osteoblast-like cells. Cell Calcium. 2006;39:435–444. [PubMed]
22. Wurm A, Pannicke T, Wiedemann P, Reichenbach A, Bringmann A. Glial cell-derived glutamate mediates autocrine cell volume regulation in the retina: Activation by VEGF. J. Neurochem. 2008;104:386–399. [PubMed]
23. Selzner N, Selzner M, Graf R, Ungethuem U, Fitz JG, Clavien PA. Water induces autocrine stimulation of tumor cell killing through ATP release and P2 receptor binding. Cell Death Differ. 2004;11(suppl. 2):S172–S180. [PubMed]
24. Yamamoto T, Suzuki Y. Role of luminal ATP in regulating electrogenic Na(+) absorption in guinea pig distal colon. Am. J. Physiol. Gastrointest. Liver Physiol. 2002;283:G300–G308. [PubMed]
25. Hovater MB, Olteanu D, Welty EA, Schwiebert EM. Purinergic signaling in the lumen of a normal nephron and in remodeled PKD encapsulated cysts. Purinergic Signal. 2008;4:109–124. [PMC free article] [PubMed]
26. Kempson SA, Edwards JM, Osborn A, Sturek M. Acute inhibition of the betaine transporter by ATP and adenosine in renal MDCK cells. Am. J. Physiol. Renal Physiol. 2008;295:F108–F117. [PMC free article] [PubMed]
27. Wang Y, Roman R, Lidofsky SD, Fitz JG. Autocrine signaling through ATP release represents a novel mechanism for cell volume regulation. Proc. Natl. Acad. Sci. U.S.A. 1996;93:12020–12025. [PMC free article] [PubMed]
28. Roman RM, Wang Y, Lidofsky SD, Feranchak AP, Lomri N, Scharschmidt BF, Fitz JG. Hepatocellular ATP-binding cassette protein expression enhances ATP release and autocrine regulation of cell volume. J. Biol. Chem. 1997;272:21970–21976. [PubMed]
29. Feranchak AP, Roman RM, Schwiebert EM, Fitz JG. Phosphatidylinositol 3-kinase contributes to cell volume regulation through effects on ATP release. J. Biol. Chem. 1998;273:14906–14911. [PubMed]
30. Feranchak AP, Fitz JG, Roman RM. Volume-sensitive purinergic signaling in human hepatocytes. J. Hepatol. 2000;33:174–182. [PubMed]
31. Roman RM, Feranchak AP, Salter KD, Wang Y, Fitz JG. Endogenous ATP release regulates Cl secretion in cultured human and rat biliary epithelial cells. Am. J. Physiol. 1999;276:G1391–G1400. [PubMed]
32. Braunstein GM, Roman RM, Clancy JP, Kudlow BA, Taylor AL, Shylonsky VG, Jovov B, Peter K, Jilling T, Ismailov II, Benos DJ, Schwiebert LM, Fitz JG, Schwiebert EM. Cystic fibrosis transmembrane conductance regulator facilitates ATP release by stimulating a separate ATP release channel for autocrine control of cell volume regulation. J. Biol. Chem. 2001;276:6621–6630. [PubMed]
33. Braunstein GM, Zsembery A, Tucker TA, Schwiebert EM. Purinergic signaling underlies CFTR control of human airway epithelial cell volume. J. Cyst. Fibros. 2004;3:99–117. [PubMed]
34. Tatur S, Groulx N, Orlov SN, Grygorczyk R. Ca2+-dependent ATP release from A549 cells involves synergistic autocrine stimulation by coreleased uridine nucleotides. J. Physiol. 2007;584:419–435. [PMC free article] [PubMed]
35. Shiga H, Tojima T, Ito E. Ca2+ signaling regulated by an ATP-dependent autocrine mechanism in astrocytes. Neuroreport. 2001;12:2619–2622. [PubMed]
36. Scemes E, Suadicani SO, Spray DC. Intercellular communication in spinal cord astrocytes: Fine tuning between gap junctions and P2 nucleotide receptors in calcium wave propagation. J. Neurosci. 2000;20:1435–1445. [PMC free article] [PubMed]
37. Jorgensen NR, Geist ST, Civitelli R, Steinberg TH. ATP- and gap junction-dependent intercellular calcium signaling in osteoblastic cells. J. Cell Biol. 1997;139:497–506. [PMC free article] [PubMed]
38. Romanello M, Pani B, Bicego M, D’Andrea P. Mechanically induced ATP release from human osteoblastic cells. Biochem. Biophys. Res. Commun. 2001;289:1275–1281. [PubMed]
39. Romanello M, Codognotto A, Bicego M, Pines A, Tell G, D’Andrea P. Autocrine/paracrine stimulation of purinergic receptors in osteoblasts: Contribution of vesicular ATP release. Biochem. Biophys. Res. Commun. 2005;331:1429–1438. [PubMed]
40. Grierson JP, Meldolesi J. Shear stress-induced [Ca2+]i transients and oscillations in mouse fibroblasts are mediated by endogenously released ATP. J. Biol. Chem. 1995;270:4451–4456. [PubMed]
41. Riddle RC, Taylor AF, Rogers JR, Donahue HJ. ATP release mediates fluid flow-induced proliferation of human bone marrow stromal cells. J. Bone Miner. Res. 2007;22:589–600. [PubMed]
42. Kawano S, Otsu K, Kuruma A, Shoji S, Yanagida E, Muto Y, Yoshikawa F, Hirayama Y, Mikoshiba K, Furuichi T. ATP autocrine/paracrine signaling induces calcium oscillations and NFAT activation in human mesenchymal stem cells. Cell Calcium. 2006;39:313–324. [PubMed]
43. Schlosser SF, Burgstahler AD, Nathanson MH. Isolated rat hepatocytes can signal to other hepatocytes and bile duct cells by release of nucleotides. Proc. Natl. Acad. Sci. U.S.A. 1996;93:9948–9953. [PMC free article] [PubMed]
44. Sauer H, Hescheler J, Wartenberg M. Mechanical strain-induced Ca(2+) waves are propagated via ATP release and purinergic receptor activation. Am. J. Physiol. Cell Physiol. 2000;279:C295–C307. [PubMed]
45. Tanneur V, Duranton C, Brand VB, Sandu CD, Akkaya C, Kasinathan RS, Gachet C, Sluyter R, Barden JA, Wiley JS, Lang F, Huber SM. Purinoceptors are involved in the induction of an osmolyte permeability in malaria-infected and oxidized human erythrocytes. FASEB J. 2006;20:133–135. [PubMed]
46. Placido R, Auricchio G, Falzoni S, Battistini L, Colizzi V, Brunetti E, Di Virgilio F, Mancino G. P2X(7) purinergic receptors and extracellular ATP mediate apoptosis of human monocytes/macrophages infected with Mycobacterium tuberculosis reducing the intracellular bacterial viability. Cell. Immunol. 2006;244:10–18. [PubMed]
47. Piccini A, Carta S, Tassi S, Lasiglié D, Fossati G, Rubartelli A. ATP is released by monocytes stimulated with pathogen-sensing receptor ligands and induces IL-1beta and IL-18 secretion in an autocrine way. Proc. Natl. Acad. Sci. U.S.A. 2008;105:8067–8072. [PMC free article] [PubMed]
48. Tsuzaki M, Bynum D, Almekinders L, Yang X, Faber J, Banes AJ. ATP modulates load-inducible IL-1beta, COX 2, and MMP-3 gene expression in human tendon cells. J. Cell. Biochem. 2003;89:556–562. [PubMed]
49. Watt WC, Lazarowski ER, Boucher RC. Cystic fibrosis transmembrane regulator-independent release of ATP. Its implications for the regulation of P2Y2 receptors in airway epithelia. J. Biol. Chem. 1998;273:14053–14058. [PubMed]
50. Yoshida H, Kobayashi D, Ohkubo S, Nakahata N. ATP stimulates interleukin-6 production via P2Y receptors in human HaCaT keratinocytes. Eur. J. Pharmacol. 2006;540:1–9. [PubMed]
51. Insel PA, Ostrom RS, Zambon AC, Hughes RJ, Balboa MA, Shehnaz D, Gregorian C, Torres B, Firestein BL, Xing M, Post SR. P2Y receptors of MDCK cells: Epithelial cell regulation by extracellular nucleotides. Clin. Exp. Pharmacol. Physiol. 2001;28:351–354. [PubMed]
52. Ostrom RS, Gregorian C, Insel PA. Cellular release of and response to ATP as key determinants of the set-point of signal transduction pathways. J. Biol. Chem. 2000;275:11735–11739. [PubMed]
53. Forrester T. A case of serendipity*. Purinergic Signal. 2008;4:93–100. [PMC free article] [PubMed]
54. Obata T. Adenosine production and its interaction with protection of ischemic and reperfusion injury of the myocardium. Life Sci. 2002;71:2083–2103. [PubMed]
55. Jensen FB, Agnisola C, Novak I. ATP release and extracellular nucleotidase activity in erythrocytes and coronary circulation of rainbow trout. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 2009;152:351–356. [PubMed]
56. Matsuka Y, Neubert JK, Maidment NT, Spigelman I. Concurrent release of ATP and substance P within guinea pig trigeminal ganglia in vivo. Brain Res. 2001;915:248–255. [PubMed]
57. Matsuka Y, Ono T, Iwase H, Mitrirattanakul S, Omoto KS, Cho T, Lam YY, Snyder B, Spigelman I. Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats. Mol. Pain. 2008;4:66. [PMC free article] [PubMed]
58. Gourine AV, Llaudet E, Dale N, Spyer KM. Release of ATP in the ventral medulla during hypoxia in rats: Role in hypoxic ventilatory response. J. Neurosci. 2005;25:1211–1218. [PubMed]
59. Zhao HB, Yu N, Fleming CR. Gap junctional hemichannel-mediated ATP release and hearing controls in the inner ear. Proc. Natl. Acad. Sci. U.S.A. 2005;102:18724–18729. [PMC free article] [PubMed]
60. Inoue K, Koizumi S, Tsuda M. The role of nucleotides in the neuron—glia communication responsible for the brain functions. J. Neurochem. 2007;102:1447–1458. [PubMed]
61. Neufeld HA, Towner RD, Pace J. A rapid method for determining ATP by the firefly luciferin-luciferase system. Experientia. 1975;31:391–392. [PubMed]
62. Sorensen CE, Novak I. Visualization of ATP release in pancreatic acini in response to cholinergic stimulus. Use of fluorescent probes and confocal microscopy. J. Biol. Chem. 2001;276:32925–32932. [PubMed]
63. Corriden R, Insel PA, Junger WG. A novel method using fluorescence microscopy for real-time assessment of ATP release from individual cells. Am. J. Physiol. Cell Physiol. 2007;293:C1420–C1425. [PubMed]
64. Imamura H, Nhat KP, Togawa H, Saito K, Iino R, Kato-Yamada Y, Nagai T, Noji H. Visualization of ATP levels inside single living cells with fluorescence resonance energy transfer-based genetically encoded indicators. Proc. Natl. Acad. Sci. U.S.A. 2009;106:15651–15656. [PMC free article] [PubMed]
65. Braunstein GM, Roman RM, Clancy JP, Kudlow BA, Taylor AL, Shylonsky VG, Jovov B, Peter K, Jilling T, Ismailov II, Benos DJ, Schwiebert LM, Fitz JG, Schwiebert EM. Cystic fibrosis transmembrane conductance regulator facilitates ATP release by stimulating a separate ATP release channel for autocrine control of cell volume regulation. J. Biol. Chem. 2001;276:6621–6630. [PubMed]
66. Sugita M, Yue Y, Foskett JK. CFTR Cl channel and CFTR-associated ATP channel: Distinct pores regulated by common gates. EMBO J. 1998;17:898–908. [PMC free article] [PubMed]
67. Kang J, Kang N, Lovatt D, Torres A, Zhao Z, Lin J, Nedergaard M. Connexin 43 hemichannels are permeable to ATP. J. Neurosci. 2008;28:4702–4711. [PMC free article] [PubMed]
68. Huang YJ, Maruyama Y, Dvoryanchikov G, Pereira E, Chaudhari N, Roper SD. The role of pannexin 1 hemichannels in ATP release and cell-cell communication in mouse taste buds. Proc. Natl. Acad. Sci. U.S.A. 2007;104:6436–6441. [PMC free article] [PubMed]
69. Bell PD, Lapointe JY, Sabirov R, Hayashi S, Peti-Peterdi J, Manabe K, Kovacs G, Okada Y. Macula densa cell signaling involves ATP release through a maxi anion channel. Proc. Natl. Acad. Sci. U.S.A. 2003;100:4322–4327. [PMC free article] [PubMed]
70. Liu HT, Toychiev AH, Takahashi N, Sabirov RZ, Okada Y. Maxi-anion channel as a candidate pathway for osmosensitive ATP release from mouse astrocytes in primary culture. Cell Res. 2008;18:558–565. [PubMed]
71. Hisadome K, Koyama T, Kimura C, Droogmans G, Ito Y, Oike M. Volume-regulated anion channels serve as an auto/paracrine nucleotide release pathway in aortic endothelial cells. J. Gen. Physiol. 2002;119:511–520. [PMC free article] [PubMed]
72. Koyama T, Kimura C, Hayashi M, Watanabe M, Karashima Y, Oike M. Hypergravity induces ATP release and actin reorganization via tyrosine phosphorylation and RhoA activation in bovine endothelial cells. Pflugers Arch. 2009;457:711–719. [PubMed]
73. Suadicani SO, Brosnan CF, Scemes E. P2X7 receptors mediate ATP release and amplification of astrocytic intercellular Ca2+ signaling. J. Neurosci. 2006;26:1378–1385. [PMC free article] [PubMed]
74. Fitz JG. Regulation of cellular ATP release. Trans. Am. Clin. Climatol. Assoc. 2007;118:199–208. [PMC free article] [PubMed]
75. Eltzschig HK, Macmanus CF, Colgan SP. Neutrophils as sources of extracellular nucleotides: Functional consequences at the vascular interface. Trends Cardiovasc. Med. 2008;18:103–107. [PMC free article] [PubMed]
76. Thompson RJ, Macvicar BA. Connexin and pannexin hemichannels of neurons and astrocytes. Channels (Austin) 2008;2:81–86. [PubMed]
77. Burnstock G. Physiology and pathophysiology of purinergic neurotransmission. Physiol. Rev. 2007;87:659–797. [PubMed]
78. Gatof D, Kilic G, Fitz JG. Vesicular exocytosis contributes to volume-sensitive ATP release in biliary cells. Am. J. Physiol. Gastrointest. Liver Physiol. 2004;286:G538–G546. [PubMed]
79. Zhang Z, Chen G, Zhou W, Song A, Xu T, Luo Q, Wang W, Gu XS, Duan S. Regulated ATP release from astrocytes through lysosome exocytosis. Nat. Cell Biol. 2007;9:945–953. [PubMed]
80. Nicke A, Bäumert HG, Rettinger J, Eichele A, Lambrecht G, Mutschler E, Schmalzing G. P2X1 and P2X3 receptors form stable trimers: A novel structural motif of ligand-gated ion channels. EMBO J. 1998;17:3016–3028. [PMC free article] [PubMed]
81. Surprenant A, North RA. Signaling at purinergic P2X receptors. Annu. Rev. Physiol. 2009;71:333–359. [PubMed]
82. Kawate T, Michel JC, Birdsong WT, Gouaux E. Crystal structure of the ATP-gated P2X(4) ion channel in the closed state. Nature. 2009;460:592–598. [PMC free article] [PubMed]
83. Ivanov AA, Costanzi S, Jacobson KA. Defining the nucleotide binding sites of P2Y receptors using rhodopsin-based homology modeling. J. Comput. Aided Mol. Des. 2006;20:417–426. [PubMed]
84. Zimmermann H. Ectonucleotidases in the nervous system; Novartis Found. Symp.; 2006; pp. 113–128. discussion 128–130, 233–237, 275–281. [PubMed]
85. Lazarowski ER, Boucher RC, Harden TK. Constitutive release of ATP and evidence for major contribution of ecto-nucleotide pyrophosphatase and nucleoside diphosphokinase to extracellular nucleotide concentrations. J. Biol. Chem. 2000;275:31061–31068. [PubMed]
86. Zimmermann H. Extracellular metabolism of ATP and other nucleotides. Naunyn Schmiedebergs Arch. Pharmacol. 2000;362:299–309. [PubMed]
87. Prosdocimo DA, Douglas DC, Romani AM, O’Neill WC, Dubyak GR. Autocrine ATP release coupled to extracellular pyrophosphate accumulation in vascular smooth muscle cells. Am. J. Physiol. Cell Physiol. 2009;296:C828–C839. [PMC free article] [PubMed]
88. Goding JW, Grobben B, Slegers H. Physiological and pathophysiological functions of the ecto-nucleotide pyrophosphatase/phosphodiesterase family. Biochim. Biophys. Acta. 2003;1638:1–19. [PubMed]
89. Hunsucker SA, Mitchell BS, Spychala J. The 5′-nucleotidases as regulators of nucleotide and drug metabolism. Pharmacol. Ther. 2005;107:1–30. [PubMed]
90. Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, Linden J. International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol. Rev. 2001;53:527–552. [PubMed]
91. Schicker K, Hussl S, Chandaka GK, Kosenburger K, Yang JW, Waldhoer M, Sitte HH, Boehm S. A membrane network of receptors and enzymes for adenine nucleotides and nucleosides. Biochim. Biophys. Acta. 2009;1793:325–334. [PubMed]
92. Xin C, Ren S, Pfeilschifter J, Huwiler A. Heterologous desensitization of the sphingosine1phosphate receptors by purinoceptor activation in renal mesangial cells. Br. J. Pharmacol. 2004;143:581–589. [PMC free article] [PubMed]
93. Capra V, Ravasi S, Accomazzo MR, Citro S, Grimoldi M, Abbracchio MP, Rovati GE. CysLT1 receptor is a target for extracellular nucleotide-induced heterologous desensitization: A possible feedback mechanism in inflammation. J. Cell Sci. 2005;118:5625–5636. [PubMed]
94. Fung CY, Cendana C, Farndale RW, Mahaut-Smith MP. Primary and secondary agonists can use P2X(1) receptors as a major pathway to increase intracellular Ca(2+) in the human platelet. J. Thromb. Haemost. 2007;5:910–917. [PMC free article] [PubMed]
95. Kaiser RA, Buxton IL. Nucleotides in the blood stream. Proc. West. Pharmacol. Soc. 2004;47:6–17. [PubMed]
96. Burnstock G, Ralevic V. New insights into the local regulation of blood flow by perivascular nerves and endothelium. Br. J. Plast. Surg. 1994;47:527–543. [PubMed]
97. Bodin P, Burnstock G. ATP-stimulated release of ATP by human endothelial cells. J. Cardiovasc. Pharmacol. 1996;27:872–875. [PubMed]
98. Malmsjø M, Chu ZM, Croft K, Erlinge D, Edvinsson L, Beilin LJ. P2Y receptor-induced EDHF vasodilatation is of primary importance for the regulation of perfusion pressure in the peripheral circulation of the rat. Acta Physiol. Scand. 2002;174:301–309. [PubMed]
99. Rosenmeier JB, Hansen J, González-Alonso J. Circulating ATP-induced vasodilatation overrides sympathetic vasoconstrictor activity in human skeletal muscle. J. Physiol. 2004;558:351–365. [PMC free article] [PubMed]
100. Winter P, Dora KA. Spreading dilatation to luminal perfusion of ATP and UTP in rat isolated small mesenteric arteries. J. Physiol. 2007;582:335–347. [PMC free article] [PubMed]
101. Mathie RT, Ralevic V, Alexander B, Burnstock G. Nitric oxide is the mediator of ATP-induced dilatation of the rabbit hepatic arterial vascular bed. Br. J. Pharmacol. 1991;103:1602–1606. [PMC free article] [PubMed]
102. Hansmann G, Ihling C, Pieske B, Bültmann R. Nucleotide-evoked relaxation of human coronary artery. Eur. J. Pharmacol. 1998;359:59–67. [PubMed]
103. Seregi A, Doll S, Schobert A, Hertting G. Functionally diverse purinergic P2Y-receptors mediate prostanoid synthesis in cultured rat astrocytes: The role of ATP-induced phosphatidyl-inositol breakdown. Eicosanoids. 1992;5(suppl.):S19–S22. [PubMed]
104. Hammer LW, Ligon AL, Hester RL. ATP-mediated release of arachidonic acid metabolites from venular endothelium causes arteriolar dilation. Am. J. Physiol. Heart Circ. Physiol. 2001;280:H2616–H2622. [PubMed]
105. Malmsjö M, Edvinsson L, Erlinge D. P2U-receptor mediated endothelium-dependent but nitric oxide-independent vascular relaxation. Br. J. Pharmacol. 1998;123:719–729. [PMC free article] [PubMed]
106. Malmsjö M, Erlinge D, Högestätt ED, Zygmunt PM. Endothelial P2Y receptors induce hyperpolarisation of vascular smooth muscle by release of endothelium-derived hyperpolarising factor. Eur. J. Pharmacol. 1999;364:169–173. [PubMed]
107. Mistry H, Gitlin JM, Mitchell JA, Hiley CR. Endothelium-dependent relaxation and endothelial hyperpolarization by P2Y receptor agonists in rat-isolated mesenteric artery. Br. J. Pharmacol. 2003;139:661–671. [PMC free article] [PubMed]
108. Bergfeld GR, Forrester T. Release of ATP from human erythrocytes in response to a brief period of hypoxia and hypercapnia. Cardiovasc. Res. 1992;26:40–47. [PubMed]
109. Ellsworth ML, Forrester T, Ellis CG, Dietrich HH. The erythrocyte as a regulator of vascular tone. Am. J. Physiol. 1995;269:H2155–H2161. [PubMed]
110. Dietrich HH, Ellsworth ML, Sprague RS, Dacey RG., Jr. Red blood cell regulation of microvascular tone through adenosine triphosphate. Am. J. Physiol. Heart Circ. Physiol. 2000;278:H1294–H1298. [PubMed]
111. Wang L, Olivecrona G, Götberg M, Olsson ML, Winzell MS, Erlinge D. ADP acting on P2Y13 receptors is a negative feedback pathway for ATP release from human red blood cells. Circ. Res. 2005;96:189–196. [PubMed]
112. Karpatkin S, Langer RM. Biochemical energetics of simulated platelet plug formation: Effect of thrombin, adenosine diphosphate, and epinephrine on intra- and extracellular adenine nucleotide kinetics. J. Clin. Invest. 1968;47:2158–2168. [PMC free article] [PubMed]
113. Marcus AJ, Broekman MJ, Drosopoulos JH, Olson KE, Islam N, Pinsky DJ, Levi R. Role of CD39 (NTPDase-1) in thromboregulation, cerebroprotection, and cardioprotection. Semin. Thromb. Hemost. 2005;31:234–246. [PubMed]
114. Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, Yang RB, Nurden P, Nurden A, Julius D, Conley PB. Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature. 2001;409:202–207. [PubMed]
115. Ahmad S, Ahmad A, White CW. Purinergic signaling and kinase activation for survival in pulmonary oxidative stress and disease. Free Radic. Biol. Med. 2006;41:29–40. [PubMed]
116. Chen Y, Corriden R, Inoue Y, Yip L, Hashiguchi N, Zinkernagel A, Nizet V, Insel PA, Junger WG. ATP release guides neutrophil chemotaxis via P2Y2 and A3 receptors. Science. 2006;314:1792–1795. [PubMed]
117. Khakh BS, North RA. P2X receptors as cell-surface ATP sensors in health and disease. Nature. 2006;442:527–532. [PubMed]
118. Corriden R, Insel PA, Junger WG. A novel method using fluorescence microscopy for real-time assessment of ATP release from individual cells. Am. J. Physiol. Cell Physiol. 2007;293:C1420–C1425. [PubMed]
119. Burnstock G. Endothelium-derived vasoconstriction by purines and pyrimidines. Circ. Res. 2008;103:1056–1057. [PubMed]
120. Schenk U, Westendorf AM, Radaelli E, Casati A, Ferro M, Fumagalli M, Verderio C, Buer J, Scanziani E, Grassi F. Purinergic control of T cell activation by ATP released through pannexin-1 hemichannels. Sci. Signal. 2008;1:ra6. [PubMed]
121. Yip L, Woehrle T, Corriden R, Hirsh M, Chen Y, Inoue Y, Ferrari V, Insel PA, Junger WG. Autocrine regulation of T-cell activation by ATP release and P2X7 receptors. FASEB J. 2009;23:1685–1693. [PMC free article] [PubMed]
122. Inscho EW. Lewis K. Dahl Memorial Lecture. Mysteries of renal autoregulation. Hypertension. 2009;53:299–306. [PMC free article] [PubMed]
123. Schliess F, Reinehr R, Häussinger D. Osmosensing and signaling in the regulation of mammalian cell function. FEBS J. 2007;274:5799–5803. [PubMed]
124. Boyer JL, Graf J, Meier PJ. Hepatic transport systems regulating pHi, cell volume, and bile secretion. Annu. Rev. Physiol. 1992;54:415–438. [PubMed]
125. Hoffmann EK, Lambert IH, Pedersen SF. Physiology of cell volume regulation in vertebrates. Physiol. Rev. 2009;89:193–277. [PubMed]
126. Roe MW, Moore AL, Lidofsky SD. Purinergic-independent calcium signaling mediates recovery from hepatocellular swelling: Implications for volume regulation. J. Biol. Chem. 2001;276:30871–30877. [PubMed]
127. Light DB, Dahlstrom PK, Gronau RT, Baumann NL. Extracellular ATP activates a P2 receptor in necturus erythrocytes during hypotonic swelling. J. Membr. Biol. 2001;182:193–202. [PubMed]
128. Light DB, Attwood AJ, Siegel C, Baumann NL. Cell swelling increases intracellular calcium in Necturus erythrocytes. J. Cell Sci. 2003;116:101–109. [PubMed]
129. Hafting T, Sand O. Purinergic activation of BK channels in clonal kidney cells (Vero cells) Acta Physiol. Scand. 2000;170:99–109. [PubMed]
130. Hafting T, Haug TM, Ellefsen S, Sand O. Hypotonic stress activates BK channels in clonal kidney cells via purinergic receptors, presumably of the P2Y subtype. Acta Physiol. (Oxf.) 2006;188:21–31. [PubMed]
131. Dezaki K, Tsumura T, Maeno E, Okada Y. Receptor-mediated facilitation of cell volume regulation by swelling-induced ATP release in human epithelial cells. Jpn. J. Physiol. 2000;50:235–241. [PubMed]
132. Van der Wijk T, De Jonge HR, Tilly BC. Osmotic cell swelling-induced ATP release mediates the activation of extracellular signal-regulated protein kinase (Erk)-1/2 but not the activation of osmo-sensitive anion channels. Biochem. J. 1999;343:579–586. [PMC free article] [PubMed]
133. Okada SF, Nicholas RA, Kreda SM, Lazarowski ER, Boucher RC. Physiological regulation of ATP release at the apical surface of human airway epithelia. J. Biol. Chem. 2006;281:22992–23002. [PMC free article] [PubMed]
134. Kimelberg HK. Increased release of excitatory amino acids by the actions of ATP and peroxynitrite on volume-regulated anion channels (VRACs) in astrocytes. Neurochem. Int. 2004;45:511–519. [PubMed]
135. Takano T, Kang J, Jaiswal JK, Simon SM, Lin JH, Yu Y, Li Y, Yang J, Dienel G, Zielke HR, Nedergaard M. Receptor-mediated glutamate release from volume sensitive channels in astrocytes. Proc. Natl. Acad. Sci. U.S.A. 2005;102:16466–16471. [PMC free article] [PubMed]
136. Zeng JW, Liu XH, Zhang JH, Wu XG, Ruan HZ. P2Y1 receptor-mediated glutamate release from cultured dorsal spinal cord astrocytes. J. Neurochem. 2008;106:2106–2118. [PubMed]
137. Rudkouskaya A, Chernoguz A, Haskew-Layton RE, Mongin AA. Two conventional protein kinase C isoforms, alpha and betaI, are involved in the ATP-induced activation of volume-regulated anion channel and glutamate release in cultured astrocytes. J. Neurochem. 2008 [PMC free article] [PubMed]
138. Rieg T, Vallon V. ATP and adenosine in the local regulation of water transport and homeostasis by the kidney. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2009;296:R419–R427. [PMC free article] [PubMed]
139. Edwards RM. Basolateral, but not apical, ATP inhibits vasopressin action in rat inner medullary collecting duct. Eur. J. Pharmacol. 2002;438:179–181. [PubMed]
140. Pochynyuk O, Bugaj V, Rieg T, Insel PA, Mironova E, Vallon V, Stockand JD. Paracrine regulation of the epithelial Na+ channel in the mammalian collecting duct by purinergic P2Y2 receptor tone. J. Biol. Chem. 2008;283:36599–36607. [PMC free article] [PubMed]
141. Zhang Y, Sands JM, Kohan DE, Nelson RD, Martin CF, Carlson NG, Kamerath CD, Ge Y, Klein JD, Kishore BK. Potential role of purinergic signaling in urinary concentration in inner medulla: Insights from P2Y2 receptor gene knockout mice. Am. J. Physiol. Renal Physiol. 2008;295:F1715–F1724. [PMC free article] [PubMed]
142. Rieg T, Bundey RA, Chen Y, Deschenes G, Junger W, Insel PA, Vallon V. Mice lacking P2Y2 receptors have salt-resistant hypertension and facilitated renal Na+ and water reabsorption. FASEB J. 2007;21:3717–3726. [PubMed]
143. Lemoli RM, Ferrari D, Fogli M, Rossi L, Pizzirani C, Forchap S, Chiozzi P, Vaselli D, Bertolini F, Foutz T, Aluigi M, Baccarani M, Di Virgilio F. Extracellular nucleotides are potent stimulators of human hematopoietic stem cells in vitro and in vivo. Blood. 2004;104:1662–1670. [PubMed]
144. Pellegatti P, Raffaghello L, Bianchi G, Piccardi F, Pistoia V, Di Virgilio F, El Khoury J. Increased level of extracellular ATP at tumor sites: In vivo imaging with plasma membrane luciferase. PLoS ONE. 2008;3:e2599. [PMC free article] [PubMed]
145. Wink MR, Lenz G, Braganhol E, Tamajusuku AS, Schwartsmann G, Sarkis JJ, Battastini AM. Altered extracellular ATP, ADP and AMP catabolism in glioma cell lines. Cancer Lett. 2003;198:211–218. [PubMed]
146. Wang Q, Wang L, Feng YH, Li X, Zeng R, Gorodeski GI. P2X7 receptor-mediated apoptosis of human cervical epithelial cells. Am. J. Physiol. Cell Physiol. 2004;287:C1349–C1358. [PubMed]
147. Coutinho-Silva R, Stahl L, Cheung KK, de Campos NE, de Oliveira Souza C, Ojcius DM, Burnstock G. P2X and P2Y purinergic receptors on human intestinal epithelial carcinoma cells: Effects of extracellular nucleotides on apoptosis and cell proliferation. Am. J. Physiol. Gastrointest. Liver Physiol. 2005;288:G1024–G1035. [PubMed]
148. Shabbir M, Ryten M, Thompson C, Mikhailidis D, Burnstock G. Characterization of calcium-independent purinergic receptor-mediated apoptosis in hormone-refractory prostate cancer. BJU Int. 2008;101:352–359. [PubMed]
149. Adinolfi E, Melchiorri L, Falzoni S, Chiozzi P, Morelli A, Tieghi A, Cuneo A, Castoldi G, Di Virgilio F, Baricordi OR. P2X7 receptor expression in evolutive and indolent forms of chronic B lymphocytic leukemia. Blood. 2002;99:706–708. [PubMed]
150. Slater M, Danieletto S, Gidley-Baird A, Teh LC, Barden JA. Early prostate cancer detected using expression of non-functional cytolytic P2X7 receptors. Histopathology. 2004;44:206–215. [PubMed]
151. Solini A, Cuccato S, Ferrari D, Santini E, Gulinelli S, Callegari MG, Dardano A, Faviana P, Madec S, Di Virgilio F, Monzani F. Increased P2X7 receptor expression and function in thyroid papillary cancer: A new potential marker of the disease? Endocrinology. 2008;149:389–396. [PubMed]
152. Nejime N, Tanaka N, Yoshihara R, Kagota S, Yoshikawa N, Nakamura K, Kunitomo M, Hashimoto M, Shinozuka K. Effect of P2 receptor on the intracellular calcium increase by cancer cells in human umbilical vein endothelial cells. Naunyn Schmiedebergs Arch. Pharmacol. 2008;377:429–436. [PubMed]
153. Hussl S, Kubista H, Boehm S. Autoregulation in PC12 cells via P2Y receptors: Evidence for non-exocytotic nucleotide release from neuroendocrine cells. Purinergic Signal. 2007;3:367–375. [PMC free article] [PubMed]
154. Housley GD, Bringmann A, Reichenbach A. Purinergic signaling in special senses. Trends Neurosci. 2009;32:128–141. [PubMed]
155. Duan S, Neary JT. P2X(7) receptors: Properties and relevance to CNS function. Glia. 2006;54:738–746. [PubMed]
156. Arthur DB, Akassoglou K, Insel PA. P2Y2 receptor activates nerve growth factor/TrkA signaling to enhance neuronal differentiation. Proc. Natl. Acad. Sci. U.S.A. 2005;102:19138–19143. [PMC free article] [PubMed]
157. Arthur DB, Akassoglou K, Insel PA. P2Y2 and TrkA receptors interact with Src family kinase for neuronal differentiation. Biochem. Biophys. Res. Commun. 2006;347:678–682. [PubMed]
158. Sugioka M, Zhou WL, Hofmann HD, Yamashita M. Involvement of P2 purinoceptors in the regulation of DNA synthesis in the neural retina of chick embryo. Int. J. Dev. Neurosci. 1999;17:135–144. [PubMed]
159. Lin JH, Takano T, Arcuino G, Wang X, Hu F, Darzynkiewicz Z, Nunes M, Goldman SA, Nedergaard M. Purinergic signaling regulates neural progenitor cell expansion and neurogenesis. Dev. Biol. 2007;302:356–366. [PMC free article] [PubMed]
160. Scemes E, Duval N, Meda P. Reduced expression of P2Y1 receptors in connexin43-null mice alters calcium signaling and migration of neural progenitor cells. J. Neurosci. 2003;23:11444–11452. [PMC free article] [PubMed]
161. Arthur DB, Taupenot L, Insel PA. Nerve growth factor-stimulated neuronal differentiation induces changes in P2 receptor expression and nucleotide-stimulated catecholamine release. J. Neurochem. 2007;100:1257–1264. [PubMed]
162. Ferrari D, Chiozzi P, Falzoni S, Dal Susino M, Collo G, Buell G, Di Virgilio F. ATP-mediated cytotoxicity in microglial cells. Neuropharmacology. 1997;36:1295–1301. [PubMed]
163. Seo DR, Kim KY, Lee YB. Interleukin-10 expression in lipopolysaccharide-activated microglia is mediated by extracellular ATP in an autocrine fashion. Neuroreport. 2004;15:1157–1161. [PubMed]
164. Seo DR, Kim SY, Kim KY, Lee HG, Moon JH, Lee JS, Lee SH, Kim SU, Lee YB. Cross talk between P2 purinergic receptors modulates extracellular ATP-mediated interleukin-10 production in rat microglial cells. Exp. Mol. Med. 2008;40:19–26. [PMC free article] [PubMed]
165. Imai M, Goepfert C, Kaczmarek E, Robson SC. CD39 modulates IL-1 release from activated endothelial cells. Biochem. Biophys. Res. Commun. 2000;270:272–278. [PubMed]
166. Solini A, Chiozzi P, Morelli A, Adinolfi E, Rizzo R, Baricordi OR, Di Virgilio F. Enhanced P2X7 activity in human fibroblasts from diabetic patients: A possible pathogenetic mechanism for vascular damage in diabetes. Arterioscler. Thromb. Vasc. Biol. 2004;24:1240–1245. [PubMed]
167. Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440:237–241. [PubMed]
168. Koshlukova SE, Araujo MW, Baev D, Edgerton M. Released ATP is an extracellular cytotoxic mediator in salivary histatin 5-induced killing of Candida albicans. Infect. Immun. 2000;68:6848–6856. [PMC free article] [PubMed]
169. Vylkova S, Sun JN, Edgerton M. The role of released ATP in killing Candida albicans and other extracellular microbial pathogens by cationic peptides. Purinergic Signal. 2007;3:91–97. [PMC free article] [PubMed]
170. Woo SR, Barletta RG, Czuprynski CJ. ATP release by infected bovine monocytes increases the intracellular survival of Mycobacterium avium subsp. paratuberculosis. Comp. Immunol. Microbiol. Infect. Dis. 2009;32:365–377. [PubMed]
171. Davis IC, Sullender WM, Hickman-Davis JM, Lindsey JR, Matalon S. Nucleotide-mediated inhibition of alveolar fluid clearance in BALB/c mice after respiratory syncytial virus infection. Am. J. Physiol. Lung Cell. Mol. Physiol. 2004;286:L112–L120. [PubMed]
172. Kolli BK, Kostal J, Zaborina O, Chakrabarty AM, Chang KP. Leishmania-released nucleoside diphosphate kinase prevents ATP-mediated cytolysis of macrophages. Mol. Biochem. Parasitol. 2008;158:163–175. [PMC free article] [PubMed]
173. Hopfe M, Henrich B, Opp A. OppA, the ecto-ATPase of Mycoplasma hominis induces ATP release and cell death in HeLa cells. BMC Microbiol. 2008;8:55. [PMC free article] [PubMed]
174. Champagne DE, Smartt CT, Ribeiro JM, James AA. The salivary gland-specific apyrase of the mosquito Aedes aegypti is a member of the 5′-nucleotidase family. Proc. Natl. Acad. Sci. U.S.A. 1995;92:694–698. [PMC free article] [PubMed]
175. Pérez de León AA, Tabachnick WJ. Apyrase activity and adenosine diphosphate induced platelet aggregation inhibition by the salivary gland proteins of Culicoides variipennis, the North American vector of bluetongue viruses. Vet. Parasitol. 1996;61:327–338. [PubMed]
176. Valenzuela JG, Belkaid Y, Rowton E, Ribeiro JM. The salivary apyrase of the blood-sucking sand fly Phlebotomus papatasi belongs to the novel Cimex family of apyrases. J. Exp. Biol. 2001;204:229–237. [PubMed]
177. Kolachala VL, Bajaj R, Chalasani M, Sitaraman SV. Purinergic receptors in gastrointestinal inflammation. Am. J. Physiol. Gastrointest. Liver Physiol. 2008;294:G401–G410. [PubMed]
178. Hussl S, Kubista H, Boehm S. Autoregulation in PC12 cells via P2Y receptors: Evidence for non-exocytotic nucleotide release from neuroendocrine cells. Purinergic Signal. 2007;3:367–375. [PMC free article] [PubMed]
179. Chen ZP, Kratzmeier M, Levy A, McArdle CA, Poch A, Day A, Mukhopadhyay AK, Lightman SL. Evidence for a role of pituitary ATP receptors in the regulation of pituitary function. Proc. Natl. Acad. Sci. U.S.A. 1995;92:5219–5223. [PMC free article] [PubMed]
180. Tomi? M, Jobin RM, Vergara LA, Stojilkovic SS. Expression of purinergic receptor channels and their role in calcium signaling and hormone release in pituitary gonadotrophs: Integration of P2 channels in plasma membrane- and endoplasmic reticulum-derived calcium oscillations. J. Biol. Chem. 1996;271:21200–21208. [PubMed]
181. Nuñez L, Villalobos C, Frawley LS. Extracellular ATP as an autocrine/paracrine regulator of prolactin release. Am. J. Physiol. 1997;272:E1117–E1123. [PubMed]
182. Caraccio N, Monzani F, Santini E, Cuccato S, Ferrari D, Callegari MG, Gulinelli S, Pizzirani C, Di Virgilio F, Ferrannini E, Solini A. Extracellular adenosine 5?-triphosphate modulates interleukin-6 production by human thyrocytes through functional purinergic P2 receptors. Endocrinology. 2005;146:3172–3178. [PubMed]
183. Pines A, Bivi N, Vascotto C, Romanello M, D’Ambrosio C, Scaloni A, Damante G, Morisi R, Filetti S, Ferretti E, Quadrifoglio F, Tell G. Nucleotide receptors stimulation by extracellular ATP controls Hsp90 expression through APE1/Ref-1 in thyroid cancer cells: A novel tumorigenic pathway. J. Cell. Physiol. 2006;209:44–55. [PubMed]
184. Hamada K, Takuwa N, Yokoyama K, Takuwa Y. Stretch activates Jun N-terminal kinase/stress-activated protein kinase in vascular smooth muscle cells through mechanisms involving autocrine ATP stimulation of purinoceptors. J. Biol. Chem. 1998;273:6334–6340. [PubMed]
185. Iwata Y, Katanosaka Y, Hisamitsu T, Wakabayashi S. Enhanced Na+/H+ exchange activity contributes to the pathogenesis of muscular dystrophy via involvement of P2 receptors. Am. J. Pathol. 2007;171:1576–1587. [PMC free article] [PubMed]
186. Grol MW, Panupinthu N, Korcok J, Sims SM, Dixon SJ. Expression, signaling, and function of P2X7 receptors in bone. Purinergic Signal. 2009;5:205–221. [PMC free article] [PubMed]
187. Orriss IR, Knight GE, Utting JC, Taylor SEB, Burnstock G, Arnett TR. Hypoxia stimulates vesicular ATP release from rat osteoblasts. J. Cell. Physiol. 2009;220:155–162. [PubMed]
188. Williams RJ, Lansford EM. The Encyclopedia of Biochemistry. Reinhold Publishing Corporation; New York: 1967.
189. Beigi R, Kobatake E, Aizawa M, Dubyak GR. Detection of local ATP release from activated platelets using cell surface-attached firefly luciferase. Am. J. Physiol. 1999;276:C267–C278. [PubMed]
190. Joseph SM, Buchakjian MR, Dubyak GR. Colocalization of ATP release sites and ecto-ATPase activity at the extracellular surface of human astrocytes. J. Biol. Chem. 2003;278:23331–23342. [PubMed]
191. Yegutkin GG. Nucleotide- and nucleoside-converting ectoenzymes: Important modulators of purinergic signalling cascade. Biochim. Biophys. Acta. 2008;1783:673–694. [PubMed]
192. Kim MY, Kuruvilla HG, Raghu S, Hennessey TM. ATP reception and chemosensory adaptation in Tetrahymena thermophila. J. Exp. Biol. 1999;202:407–416. [PubMed]
193. Wood CR, Hennessey TM. PPNDS is an agonist, not an antagonist, for the ATP receptor of Paramecium. J. Exp. Biol. 2003;206:627–636. [PubMed]
194. Agboh KC, Webb TE, Evans RJ, Ennion SJ. Functional characterization of a P2X receptor from Schistosoma mansoni. J. Biol. Chem. 2004;279:41650–41657. [PubMed]
195. Fountain SJ, Parkinson K, Young MT, Cao L, Thompson CR, North RA. An intracellular P2X receptor required for osmoregulation in Dictyostelium discoideum. Nature. 2007;448:200–203. [PMC free article] [PubMed]
196. Bagorda A, Parent CA. Eukaryotic chemotaxis at a glance. J. Cell Sci. 2008;121:2621–2624. [PubMed]
197. Elliott MR, Chekeni FB, Trampont PC, Lazarowski ER, Kadl A, Walk SF, Park D, Woodson RI, Ostankovich M, Sharma P, Lysiak JJ, Harden TK, Leitinger N, Ravichandran KS. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature. 2009;461:282–286. [PMC free article] [PubMed]
198. Dranoff JA, O’Neill AF, Franco AM, Cai SY, Connolly GC, Ballatori N, Boyer JL, Nathanson MH. A primitive ATP receptor from the little skate Raja erinacea. J. Biol. Chem. 2000;275:30701–30706. [PubMed]
199. Carabelli V, Carra I, Carbone E. Localized secretion of ATP and opioids revealed through single Ca2+ channel modulation in bovine chromaffin cells. Neuron. 1998;20:1255–1268. [PubMed]
200. Ferrari D, Chiozzi P, Falzoni S, Hanau S, Di Virgilio F. Purinergic modulation of interleukin-1 beta release from microglial cells stimulated with bacterial endotoxin. J. Exp. Med. 1997;185:579–582. [PMC free article] [PubMed]
201. Sanz JM, Chiozzi P, Ferrari D, Colaianna M, Idzko M, Falzoni S, Fellin R, Trabace L, Di Virgilio F. Activation of microglia by amyloid β requires P2X7 receptor expression. J. Immunol. 2009;182:4378–4385. [PubMed]
202. Kim SY, Moon JH, Lee HG, Kim SU, Lee YB. ATP released from beta-amyloid-stimulated microglia induces reactive oxygen species production in an autocrine fashion. Exp. Mol. Med. 2007;39:820–827. [PubMed]
203. Gerasimovskaya EV, Ahmad S, White CW, Jones PL, Carpenter TC, Stenmark KR. Extracellular ATP is an autocrine/paracrine regulator of hypoxia-induced adventitial fibroblast growth. Signaling through extracellular signal-regulated kinase-1/2 and the Egr-1 transcription factor. J. Biol. Chem. 2002;277:44638–44650. [PubMed]
204. Kiefmann R, Islam MN, Lindert J, Parthasarathi K, Bhattacharya J. Paracrine purinergic signaling determines lung endothelial nitric oxide production. Am. J. Physiol. Lung Cell. Mol. Physiol. 2009;296:L901–L910. [PMC free article] [PubMed]
205. Kalinowski L, Dobrucki LW, Szczepanska-Konkel M, Jankowski M, Martyniec L, Angielski S, Malinski T. Third-generation beta-blockers stimulate nitric oxide release from endothelial cells through ATP efflux: A novel mechanism for antihypertensive action. Circulation. 2003;107:2747–2752. [PubMed]
206. Baricordi OR, Melchiorri L, Adinolfi E, Falzoni S, Chiozzi P, Buell G, Di Virgilio F. Increased proliferation rate of lymphoid cells transfected with the P2X(7) ATP receptor. J. Biol. Chem. 1999;274:33206–33208. [PubMed]
207. Tolhurst G, Vial C, Léon C, Gachet C, Evans RJ, Mahaut-Smith MP. Interplay between P2Y(1), P2Y(12), and P2X(1) receptors in the activation of megakaryocyte cation influx currents by ADP: Evidence that the primary megakaryocyte represents a fully functional model of platelet P2 receptor signaling. Blood. 2005;106:1644–1651. [PubMed]
208. McNamara N, Khong A, McKemy D, Caterina M, Boyer J, Julius D, Basbaum C. ATP transduces signals from ASGM1, a glycolipid that functions as a bacterial receptor. Proc. Natl. Acad. Sci. U.S.A. 2001;98:9086–9091. [PMC free article] [PubMed]
209. Adinolfi E, Callegari MG, Ferrari D, Bolognesi C, Minelli M, Wieckowski MR, Pinton P, Rizzuto R, Di Virgilio F. Basal activation of the P2X7 ATP receptor elevates mitochondrial calcium and potential, increases cellular ATP levels, and promotes serum-independent growth. Mol. Biol. Cell. 2005;16:3260–3272. [PMC free article] [PubMed]
210. Ma HP, Li L, Zhou ZH, Eaton DC, Warnock DG. ATP masks stretch activation of epithelial sodium channels in A6 distal nephron cells. Am. J. Physiol. Renal Physiol. 2002;282:F501–F505. [PubMed]
211. Gorelik J, Zhang Y, Sánchez D, Shevchuk A, Frolenkov G, Lab M, Klenerman D, Edwards C, Korchev Y. Aldosterone acts via an ATP autocrine/paracrine system: The Edelman ATP hypothesis revisited. Proc. Natl. Acad. Sci. U.S.A. 2005;102:15000–15005. [PMC free article] [PubMed]
212. Hellman B, Dansk H, Grapengiesser E. Pancreatic beta-cells communicate via intermittent release of ATP. Am. J. Physiol. Endocrinol. Metab. 2004;286:E759–E765. [PubMed]
213. Minagawa N, Nagata J, Shibao K, Masyuk AI, Gomes DA, Rodrigues MA, Lesage G, Akiba Y, Kaunitz JD, Ehrlich BE, Larusso NF, Nathanson MH. Cyclic AMP regulates bicarbonate secretion in cholangiocytes through release of ATP into bile. Gastroenterology. 2007;133:1592–1602. [PMC free article] [PubMed]
214. Sauer H, Stanelle R, Hescheler J, Wartenberg M. The DC electrical-field-induced Ca(2+) response and growth stimulation of multicellular tumor spheroids are mediated by ATP release and purinergic receptor stimulation. J. Cell Sci. 2002;115:3265–3273. [PubMed]
215. Schwiebert EM, Egan ME, Hwang TH, Fulmer SB, Allen SS, Cutting GR, Guggino WB. CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATP. Cell. 1995;81:1063–1073. [PubMed]
216. Ito Y, Son M, Sato S, Ishikawa T, Kondo M, Nakayama S, Shimokata K, Kume H. ATP release triggered by activation of the Ca2+-activated K+ channel in human airway Calu-3 cells. Am. J. Respir. Cell Mol. Biol. 2004;30:388–395. [PubMed]
217. Corriden R, Insel PA. Basal release of ATP: An autocrine-paracrine mechanism for cell regulation. Sci. Signal. 2010;3:re1. [PMC free article] [PubMed]
PubReader format: click here to try


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...