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J Clin Invest. Aug 1995; 96(2): 657–664.
PMCID: PMC185246

Rat kidney thromboxane receptor: molecular cloning, signal transduction, and intrarenal expression localization.


Thromboxane (TX) plays important roles in control of renal hemodynamics and water and electrolyte metabolism, and is involved in the pathophysiology of many renal diseases. The aim of the present study is to isolate a rat kidney cDNA encoding functional TX receptor, and to reveal its intrarenal expression localization. A clone (rTXR2) was isolated from a rat kidney cDNA library by a homology screening approach. rTXR2 was shown to encode the amino acid sequence containing seven transmembrane spanning domains representing rat (r) TX receptor. The membrane from COS-7 cells transiently transfected with rTXR2 cDNA was shown to be specifically bound by a thromboxane receptor antagonist, SQ29548. Either in Xenopus oocyte expression or in transfected COS-7 cells, rTX receptor was shown to be linked with Ca2+ messenger system. TX receptor-mediated increase in cytosolic Ca2+ was also observed in cultured glomerular mesangial cells. In situ hybridization showed that rTX receptor mRNA was detected in renal glomeruli, smooth muscle cells in renal arterioles, and transitional cell epithelium of renal pelvis. Reverse transcription linked to PCR applied to microdissected nephron segments indicated the presence of rTX receptor mRNA exclusively in the glomerulus. In conclusion, we have cloned a functional rat kidney TX receptor, which is expressed specifically in renal glomerulus, arterial smooth muscle cells, and transitional cell epithelium of renal pelvis. The present study will provide important insights into the etiology and pathophysiology of renal diseases with relation to TX metabolism.

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  • Cirino M, Morton H, MacDonald C, Hadden J, Ford-Hutchinson AW. Thromboxane A2 and prostaglandin endoperoxide analogue effects on porcine renal blood flow. Am J Physiol. 1990 Jan;258(1 Pt 2):F109–F114. [PubMed]
  • Welch WJ, Wilcox CS. Potentiation of tubuloglomerular feedback in the rat by thromboxane mimetic. Role of macula densa. J Clin Invest. 1992 Jun;89(6):1857–1865. [PMC free article] [PubMed]
  • Kelley VE, Sneve S, Musinski S. Increased renal thromboxane production in murine lupus nephritis. J Clin Invest. 1986 Jan;77(1):252–259. [PMC free article] [PubMed]
  • Patrono C, Ciabattoni G, Remuzzi G, Gotti E, Bombardieri S, Di Munno O, Tartarelli G, Cinotti GA, Simonetti BM, Pierucci A. Functional significance of renal prostacyclin and thromboxane A2 production in patients with systemic lupus erythematosus. J Clin Invest. 1985 Sep;76(3):1011–1018. [PMC free article] [PubMed]
  • Remuzzi G, Imberti L, Rossini M, Morelli C, Carminati C, Cattaneo GM, Bertani T. Increased glomerular thromboxane synthesis as a possible cause of proteinuria in experimental nephrosis. J Clin Invest. 1985 Jan;75(1):94–101. [PMC free article] [PubMed]
  • Coffman TM, Yarger WE, Klotman PE. Functional role of thromboxane production by acutely rejecting renal allografts in rats. J Clin Invest. 1985 Apr;75(4):1242–1248. [PMC free article] [PubMed]
  • Rinder CA, Halushka PV, Sens MA, Ploth DW. Thromboxane A2 receptor blockade improves renal function and histopathology in the post-obstructive kidney. Kidney Int. 1994 Jan;45(1):185–192. [PubMed]
  • Takahashi K, Schreiner GF, Yamashita K, Christman BW, Blair I, Badr KF. Predominant functional roles for thromboxane A2 and prostaglandin E2 during late nephrotoxic serum glomerulonephritis in the rat. J Clin Invest. 1990 Jun;85(6):1974–1982. [PMC free article] [PubMed]
  • Spurney RF, Fan PY, Ruiz P, Sanfilippo F, Pisetsky DS, Coffman TM. Thromboxane receptor blockade reduces renal injury in murine lupus nephritis. Kidney Int. 1992 Apr;41(4):973–982. [PubMed]
  • Stahl RA, Thaiss F, Wenzel U, Schoeppe W, Helmchen U. A rat model of progressive chronic glomerular sclerosis: the role of thromboxane inhibition. J Am Soc Nephrol. 1992 May;2(11):1568–1577. [PubMed]
  • Perico N, Rossini M, Imberti O, Malanchini B, Cornejo RP, Gaspari F, Bertani T, Remuzzi G. Thromboxane receptor blockade attenuates chronic cyclosporine nephrotoxicity and improves survival in rats with renal isograft. J Am Soc Nephrol. 1992 Mar;2(9):1398–1404. [PubMed]
  • Hirata M, Hayashi Y, Ushikubi F, Yokota Y, Kageyama R, Nakanishi S, Narumiya S. Cloning and expression of cDNA for a human thromboxane A2 receptor. Nature. 1991 Feb 14;349(6310):617–620. [PubMed]
  • Raychowdhury MK, Yukawa M, Collins LJ, McGrail SH, Kent KC, Ware JA. Alternative splicing produces a divergent cytoplasmic tail in the human endothelial thromboxane A2 receptor. J Biol Chem. 1994 Jul 29;269(30):19256–19261. [PubMed]
  • Namba T, Sugimoto Y, Hirata M, Hayashi Y, Honda A, Watabe A, Negishi M, Ichikawa A, Narumiya S. Mouse thromboxane A2 receptor: cDNA cloning, expression and northern blot analysis. Biochem Biophys Res Commun. 1992 May 15;184(3):1197–1203. [PubMed]
  • Folger WH, Halushka PV, Wilcox CS, Guzman NJ. Characterization of rat glomerular thromboxane A2 receptors: comparison to rat platelets. Eur J Pharmacol. 1992 Sep 1;227(1):71–78. [PubMed]
  • Mene' P, Simonson MS, Dunn MJ. Eicosanoids, mesangial contraction, and intracellular signal transduction. Tohoku J Exp Med. 1992 Jan;166(1):57–73. [PubMed]
  • Spurney RF, Onorato JJ, Albers FJ, Coffman TM. Thromboxane binding and signal transduction in rat glomerular mesangial cells. Am J Physiol. 1993 Feb;264(2 Pt 2):F292–F299. [PubMed]
  • Miki I, Kishibayashi N, Nonaka H, Ohshima E, Takami H, Obase H, Ishii A. Effects of KW-3635, a novel dibenzoxepin derivative of a selective thromboxane A2 antagonist, on human, guinea pig and rat platelets. Jpn J Pharmacol. 1992 Jul;59(3):357–364. [PubMed]
  • Murphy TJ, Alexander RW, Griendling KK, Runge MS, Bernstein KE. Isolation of a cDNA encoding the vascular type-1 angiotensin II receptor. Nature. 1991 May 16;351(6323):233–236. [PubMed]
  • Abe T, Sugihara H, Nawa H, Shigemoto R, Mizuno N, Nakanishi S. Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca2+ signal transduction. J Biol Chem. 1992 Jul 5;267(19):13361–13368. [PubMed]
  • Scharschmidt LA, Dunn MJ. Prostaglandin synthesis by rat glomerular mesangial cells in culture. Effects of angiotensin II and arginine vasopressin. J Clin Invest. 1983 Jun;71(6):1756–1764. [PMC free article] [PubMed]
  • Sato M, Abe K, Takeuchi K, Matsui K, Yasujima M, Fang SN, Kanazawa M, Yoshida K, Kimura T, Yoshinaga K. Cyclic GMP accumulation by atriopeptins in cultured rat renal and vascular smooth muscle cells. Tohoku J Exp Med. 1988 Apr;154(4):399–411. [PubMed]
  • Takeuchi K, Alexander RW, Nakamura Y, Tsujino T, Murphy TJ. Molecular structure and transcriptional function of the rat vascular AT1a angiotensin receptor gene. Circ Res. 1993 Oct;73(4):612–621. [PubMed]
  • Takeuchi K, Abe T, Takahashi N, Abe K. Molecular cloning and intrarenal localization of rat prostaglandin E2 receptor EP3 subtype. Biochem Biophys Res Commun. 1993 Jul 30;194(2):885–891. [PubMed]
  • Takeuchi K, Abe K, Yasujima M, Sato M, Maeyama K, Watanabe T, Sato S, Inaba H, Yoshinaga K. Phosphoinositide hydrolysis and calcium mobilization induced by vasopressin and angiotensin II in cultured vascular smooth muscle cells. Tohoku J Exp Med. 1992 Jan;166(1):107–122. [PubMed]
  • Tsien RY, Pozzan T, Rink TJ. Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator. J Cell Biol. 1982 Aug;94(2):325–334. [PMC free article] [PubMed]
  • Grynkiewicz G, Poenie M, Tsien RY. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed]
  • Takahashi N, Kondo Y, Ito O, Igarashi Y, Omata K, Abe K. Vasopressin stimulates Cl- transport in ascending thin limb of Henle's loop in hamster. J Clin Invest. 1995 Apr;95(4):1623–1627. [PMC free article] [PubMed]
  • Takeuchi K, Takahashi N, Abe T, Abe K. Two isoforms of the rat kidney EP3 receptor derived by alternative RNA splicing: intrarenal expression co-localization. Biochem Biophys Res Commun. 1994 Mar 15;199(2):834–840. [PubMed]
  • Terada Y, Tomita K, Nonoguchi H, Marumo F. PCR localization of angiotensin II receptor and angiotensinogen mRNAs in rat kidney. Kidney Int. 1993 Jun;43(6):1251–1259. [PubMed]
  • Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. [PubMed]
  • von Heijne G. Patterns of amino acids near signal-sequence cleavage sites. Eur J Biochem. 1983 Jun 1;133(1):17–21. [PubMed]
  • Funk CD, Furci L, Moran N, Fitzgerald GA. Point mutation in the seventh hydrophobic domain of the human thromboxane A2 receptor allows discrimination between agonist and antagonist binding sites. Mol Pharmacol. 1993 Nov;44(5):934–939. [PubMed]
  • Hubbard SC, Ivatt RJ. Synthesis and processing of asparagine-linked oligosaccharides. Annu Rev Biochem. 1981;50:555–583. [PubMed]
  • Kemp BE, Pearson RB. Protein kinase recognition sequence motifs. Trends Biochem Sci. 1990 Sep;15(9):342–346. [PubMed]
  • Dascal N. The use of Xenopus oocytes for the study of ion channels. CRC Crit Rev Biochem. 1987;22(4):317–387. [PubMed]
  • Suryanarayana S, Daunt DA, Von Zastrow M, Kobilka BK. A point mutation in the seventh hydrophobic domain of the alpha 2 adrenergic receptor increases its affinity for a family of beta receptor antagonists. J Biol Chem. 1991 Aug 15;266(23):15488–15492. [PubMed]
  • Savarese TM, Fraser CM. In vitro mutagenesis and the search for structure-function relationships among G protein-coupled receptors. Biochem J. 1992 Apr 1;283(Pt 1):1–19. [PMC free article] [PubMed]
  • Spiegel AM, Shenker A, Weinstein LS. Receptor-effector coupling by G proteins: implications for normal and abnormal signal transduction. Endocr Rev. 1992 Aug;13(3):536–565. [PubMed]
  • Shenker A, Goldsmith P, Unson CG, Spiegel AM. The G protein coupled to the thromboxane A2 receptor in human platelets is a member of the novel Gq family. J Biol Chem. 1991 May 15;266(14):9309–9313. [PubMed]
  • Miki I, Kase H, Ishii A. Differences in activities of thromboxane A2 receptor antagonists in smooth muscle cells. Eur J Pharmacol. 1992 Oct 1;227(2):199–204. [PubMed]
  • Paxton WG, Runge M, Horaist C, Cohen C, Alexander RW, Bernstein KE. Immunohistochemical localization of rat angiotensin II AT1 receptor. Am J Physiol. 1993 Jun;264(6 Pt 2):F989–F995. [PubMed]
  • Coppola S, Frömter E. An electrophysiological study of angiotensin II regulation of Na-HCO3 cotransport and K conductance in renal proximal tubules. I. Effect of picomolar concentrations. Pflugers Arch. 1994 May;427(1-2):143–150. [PubMed]
  • Wolf G, Neilson EG. Angiotensin II as a renal growth factor. J Am Soc Nephrol. 1993 Mar;3(9):1531–1540. [PubMed]
  • Burch RM, Knapp DR, Halushka PV. Vasopressin-stimulated water flow is decreased by thromboxane synthesis inhibition or antagonism. Am J Physiol. 1980 Aug;239(2):F160–F166. [PubMed]

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