Logo of jphysiolThe Journal of Physiology SiteMembershipSubmissionJ Physiol
J Physiol. Jan 1986; 370: 75–90.
PMCID: PMC1192669

Adenosine agonists reduce voltage-dependent calcium conductance of mouse sensory neurones in cell culture.


Adenosine and several of its analogues produced a concentration-dependent shortening of calcium-dependent action potential (c.a.p.) duration of mouse dorsal root ganglion (d.r.g.) neurones in dissociated cell culture. The following rank order of potency was obtained: N6-(L-phenylisopropyl)adenosine greater than N6-(D-phenylisopropyl)adenosine greater than N6-cyclohexyladenosine greater than 2-chloroadenosine much greater than 1-methylisoguanosine greater than adenosine. Effects of adenosine agonists on c.a.p. duration were blocked by methylxanthine adenosine antagonists. Adenosine monophosphate (AMP) and cyclic AMP shortened c.a.p.s in d.r.g. neurones, while ATP also depolarized cells. Voltage-clamp analysis revealed that the effect arose from reduction of a voltage-dependent calcium conductance. Adenosine agonists reduced depolarization-evoked inward currents but did not alter membrane conductance following blockade of calcium channels by cadmium. Additionally, adenosine reduced the instantaneous current-voltage slope (chord conductance) during step commands that produced maximal activation of voltage-dependent calcium conductance. If effects of adenosine on neuronal somata and synaptic terminals are similar, adenosine agonists may inhibit neurotransmitter release in the central nervous system by inhibiting a voltage-dependent calcium conductance. Since effects of adenosine agonists did not correspond with their relative potencies as modulators of adenylate cyclase activity or inhibitors of neurotransmitter release in peripheral tissues, a novel adenosine receptor may be involved in regulation of this conductance.

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Selected References

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  • Bruns RF, Daly JW, Snyder SH. Adenosine receptors in brain membranes: binding of N6-cyclohexyl[3H]adenosine and 1,3-diethyl-8-[3H]phenylxanthine. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5547–5551. [PMC free article] [PubMed]
  • Collis MG. Evidence for an A1-adenosine receptor in the guinea-pig atrium. Br J Pharmacol. 1983 Jan;78(1):207–212. [PMC free article] [PubMed]
  • Daum PR, Hill SJ, Young JM. Histamine H1-agonist potentiation of adenosine-stimulated cyclic AMP accumulation in slices of guinea-pig cerebral cortex: comparison of response and binding parameters. Br J Pharmacol. 1982 Oct;77(2):347–357. [PMC free article] [PubMed]
  • Ebersolt C, Premont J, Prochiantz A, Perez M, Bockaert J. Inhibition of brain adenylate cyclase by A1 adenosine receptors: pharmacological characteristics and locations. Brain Res. 1983 May 9;267(1):123–129. [PubMed]
  • Ebstein RP, Daly JW. Release of norepinephrine and dopamine from brain vesicular preparations: effects of adenosine analogues. Cell Mol Neurobiol. 1982 Sep;2(3):193–204. [PubMed]
  • Fredholm BB, Hedqvist P. Modulation of neurotransmission by purine nucleotides and nucleosides. Biochem Pharmacol. 1980 Jun 15;29(12):1635–1643. [PubMed]
  • Fredholm BB, Jonzon B, Lindgren E. Inhibition of noradrenaline release from hippocampal slices by a stable adenosine analogue. Acta Physiol Scand Suppl. 1983;515:7–10. [PubMed]
  • Fredholm BB, Jonzon B, Lindgren E, Lindström K. Adenosine receptors mediating cyclic AMP production in the rat hippocampus. J Neurochem. 1982 Jul;39(1):165–175. [PubMed]
  • Ginsborg BL, Hirst GD. The effect of adenosine on the release of the transmitter from the phrenic nerve of the rat. J Physiol. 1972 Aug;224(3):629–645. [PMC free article] [PubMed]
  • Harms HH, Wardeh G, Mulder AH. Adenosine modulates depolarization-induced release of 3H-noradrenaline from slices of rat brain neocortex. Eur J Pharmacol. 1978 Jun 1;49(3):305–308. [PubMed]
  • Henon BK, McAfee DA. The ionic basis of adenosine receptor actions on post-ganglionic neurones in the rat. J Physiol. 1983 Mar;336:607–620. [PMC free article] [PubMed]
  • Heyer EJ, Macdonald RL. Barbiturate reduction of calcium-dependent action potentials: correlation with anesthetic action. Brain Res. 1982 Mar 18;236(1):157–171. [PubMed]
  • Heyer EJ, Macdonald RL. Calcium- and sodium-dependent action potentials of mouse spinal cord and dorsal root ganglion neurons in cell culture. J Neurophysiol. 1982 Apr;47(4):641–655. [PubMed]
  • Hollins C, Stone TW. Adenosine inhibition of gamma-aminobutyric acid release from slices of rat cerebral cortex. Br J Pharmacol. 1980 May;69(1):107–112. [PMC free article] [PubMed]
  • Jahr CE, Jessell TM. ATP excites a subpopulation of rat dorsal horn neurones. Nature. 1983 Aug 25;304(5928):730–733. [PubMed]
  • Jamieson D, Davis P. Inhibition of nerve-mediated contractions in isolated guinea-pig ileum by 1-methylisoguanosine, a novel purine from a sponge. Eur J Pharmacol. 1980 Oct 17;67(2-3):295–300. [PubMed]
  • Jones TR, Lefcoe NM, Hamilton JT. Pharmacological study of adenosine and related compounds on isolated guinea pig trachea: evidence for more than one type of purine receptor. Can J Physiol Pharmacol. 1980 Nov;58(11):1356–1365. [PubMed]
  • Kuroda Y, Saito M, Kobayashi K. Concomitant changes in cyclic AMP level and postsynaptic potentials of olfactory cortex slices induced by adenosine derivatives. Brain Res. 1976 Jun 4;109(1):196–201. [PubMed]
  • Londos C, Cooper DM, Wolff J. Subclasses of external adenosine receptors. Proc Natl Acad Sci U S A. 1980 May;77(5):2551–2554. [PMC free article] [PubMed]
  • Michaelis ML, Michaelis EK, Myers SL. Adenosine modulation of synaptosomal dopamine release. Life Sci. 1979 May 28;24(22):2083–2092. [PubMed]
  • Mudge AW, Leeman SE, Fischbach GD. Enkephalin inhibits release of substance P from sensory neurons in culture and decreases action potential duration. Proc Natl Acad Sci U S A. 1979 Jan;76(1):526–530. [PMC free article] [PubMed]
  • Oakes SG, Pozos RS. Electrophysiologic effects of acute ethanol exposure. II. Alterations in the calcium component of action potentials from sensory neurons in dissociated culture. Brain Res. 1982 Nov;281(3):251–255. [PubMed]
  • Okada Y, Ozawa S. Inhibitory action of adenosine on synaptic transmission in the hippocampus of the guinea pig in vitro. Eur J Pharmacol. 1980 Dec 19;68(4):483–492. [PubMed]
  • Pedata F, Antonelli T, Lambertini L, Beani L, Pepeu G. Effect of adenosine, adenosine triphosphate, adenosine deaminase, dipyridamole and aminophylline on acetylcholine release from electrically-stimulated brain slices. Neuropharmacology. 1983 May;22(5):609–614. [PubMed]
  • Phillis JW, Edstrom JP, Kostopoulos GK, Kirkpatrick JR. Effects of adenosine and adenine nucleotides on synaptic transmission in the cerebral cortex. Can J Physiol Pharmacol. 1979 Nov;57(11):1289–1312. [PubMed]
  • Phillis JW. Evidence for an A2-like adenosine receptor on cerebral cortical neurons. J Pharm Pharmacol. 1982 Jul;34(7):453–454. [PubMed]
  • Phillis JW, Wu PH. The effect of various centrally active drugs on adenosine uptake by the central nervous system. Comp Biochem Physiol C. 1982;72(2):179–187. [PubMed]
  • Proctor WR, Dunwiddie TV. Adenosine inhibits calcium spikes in hippocampal pyramidal neurons in vitro. Neurosci Lett. 1983 Feb 21;35(2):197–201. [PubMed]
  • Ransom BR, Neale E, Henkart M, Bullock PN, Nelson PG. Mouse spinal cord in cell culture. I. Morphology and intrinsic neuronal electrophysiologic properties. J Neurophysiol. 1977 Sep;40(5):1132–1150. [PubMed]
  • Reddington M, Lee KS, Schubert P. An A1-adenosine receptor, characterized by [3H] cyclohexyladenosine binding, mediates the depression of evoked potentials in a rat hippocampal slice preparation. Neurosci Lett. 1982 Mar 5;28(3):275–279. [PubMed]
  • Ribeiro JA, Sá-Almeida AM, Namorado JM. Adenosine and adenosine triphosphate decrease 45Ca uptake by synaptosomes stimulated by potassium. Biochem Pharmacol. 1979 Apr 15;28(8):1297–1300. [PubMed]
  • Sawynok J, Jhamandas KH. Inhibition of acetylcholine release from cholinergic nerves by adenosine, adenine nucleotides and morphine: antagonism by theophylline. J Pharmacol Exp Ther. 1976 May;197(2):379–390. [PubMed]
  • Scholfield CN. Depression of evoked potentials in brain slices by adenosine compounds. Br J Pharmacol. 1978 Jun;63(2):239–244. [PMC free article] [PubMed]
  • Schrader J, Rubio R, Berne RM. Inhibition of slow action potentials of guinea pig atrial muscle by adenosine: a possible effect on Ca2+ influx. J Mol Cell Cardiol. 1975 Jun;7(6):427–433. [PubMed]
  • Schubert P, Mitzdorf U. Analysis and quantitative evaluation of the depressive effect of adenosine on evoked potentials in hippocampal slices. Brain Res. 1979 Aug 17;172(1):186–190. [PubMed]
  • Segal M. Intracellular analysis of a postsynaptic action of adenosine in the rat hippocampus. Eur J Pharmacol. 1982 Apr 23;79(3-4):193–199. [PubMed]
  • Skerritt JH, Johnston GA, Chow SC. Interactions of the anticonvulsant carbamazepine with adenosine receptors. 2. Pharmacological studies. Epilepsia. 1983 Oct;24(5):643–650. [PubMed]
  • Stone TW. Physiological roles for adenosine and adenosine 5'-triphosphate in the nervous system. Neuroscience. 1981;6(4):523–555. [PubMed]
  • Stone TW. Purine receptors involved in the depression of neuronal firing in cerebral cortex. Brain Res. 1982 Sep 30;248(2):367–370. [PubMed]
  • Su C. Purinergic neurotransmission and neuromodulation. Annu Rev Pharmacol Toxicol. 1983;23:397–411. [PubMed]
  • van Calker D, Müller M, Hamprecht B. Adenosine inhibits the accumulation of cyclic AMP in cultured brain cells. Nature. 1978 Dec 21;276(5690):839–841. [PubMed]
  • Werz MA, Macdonald RL. Opioid peptides decrease calcium-dependent action potential duration of mouse dorsal root ganglion neurons in cell culture. Brain Res. 1982 May 6;239(1):315–321. [PubMed]
  • Wilson WA, Goldner MM. Voltage clamping with a single microelectrode. J Neurobiol. 1975 Jul;6(4):411–422. [PubMed]
  • Wu PH, Phillis JW, Thierry DL. Adenosine receptor agonists inhibit K+-evoked Ca2+ uptake by rat brain cortical synaptosomes. J Neurochem. 1982 Sep;39(3):700–708. [PubMed]

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