Summary
Endothelial cells possess P2 purinoceptors of the P2Y subclass. These are coupled to the generation of inositol trisphosphate and hence the mobilization of intracellular calcium stores. P2Y receptor-mediated changes in intracellular ionized calcium have been followed in detail in cell populations and in individual endothelial cells, and consist of a second phase of calcium elevation requiring calcium entry, in addition to the first transient rise which is due to discharge from internal stores. Synthesis of prostacyclin, a potent vasodilator and inhibitor of platelet function, is driven by the first phase of the calcium response. The properties of the second phase of the calcium response, in contrast, are consistent with a causal role for this phase in the synthesis of nitric oxide (endothelium-derived relaxing factor), although this has yet to be established directly.
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References
Burnstock G (1978) A basis for distinguishing two types of purinergic receptor. In: Bolis C, Sträub RW (eds) Cell membrane receptors for drugs and hormones. Raven, New York, pp 107–118.
Gordon JL (1986) Extracellular ATP: Effects, sources and fate. Biochem J 233:309–319.
Pearson JD, Gordon JL (1979) Vascular endothelial and smooth muscle cells in culture selectively release adenine nucleotides. Nature 281:384–386.
LeRoy EC, Ager A, Gordon JL (1984) Effects of neutrophil elastase and other proteases on porcine aortic endothelial prostaglandin I2 production, adenine nucleotide release and responses to vasoactive agents. J Clin Invest 74:1001–1010.
Olsson R, Pearson JD (1990) Cardiovascular purinoceptors. Physiol Rev 70:761–845.
Pearson JD, Gordon JL (1985) Nucleotide metabolism by endothelium. Ann Rev Physiol 47:617–627.
Schrader J, Borst MM, Kelm M, Bading B, Burning KF (1990) Formation of adenosine in the heart from extracellular adenine nucleotides. In: Jacobson KA, Daly JW, Manganiello V (eds) Purines in cellular signalling. Springer-Verlag, New York, pp 33–40.
Winbury MM, Papierski DH, Hemmer ML, Hambourger WE (1953) Coronary dilator action of the adenine-ATP series. J Pharmacol Exp Ther 109:255–260.
Newby AC, Worku Y, Meghji P (1987). Critical evaluation of the role of ecto-and cytosolic 5′-nucleotidase in adenosine formation. In: Gerlach E, Becker BF (eds) Topics and perspectives in adenosine research. Springer-Verlag, Berlin, pp 155–168.
De Mey JG, Vanhoutte PM (1981) Role of the intima in the cholinergic and purinergic relaxation of isolated canine femoral arteries. J Physiol (Lond) 316:347–355.
Furchgott RF (1984) The role of the endothelium in the responses of vascluar smooth muscle to drugs. Annu Rev Pharmacol Toxicol 24:175–197.
Palmer RMJ, Ashton DS, Moncada S (1988) Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333:664–666.
Martin W, Cusack NJ, Carleton JS, Gordon JL (1985) Specificity of P2-purinoceptor that mediates endothelium-dependent relaxation of the pig aorta. Eur J Pharmacol 108:295–299.
Burnstock G, Kennedy C (1985) Is there a basis for distinguishing two types of P2-purinoceptor? Gen Pharmacol 16:433–440.
Pearson JD, Slakey LL, Gordon JL (1983) Stimulation of prostacyclin production through purinoceptors on cultured porcine aortic endothelial cells. Biochem J 214:273–276.
Pearson JD, Carter TD (1989) Transduction of purinoceptor-mediated endothelial cell responses. In: Catravas JD, Gillis CN (eds) Vascular endothelium. Receptors and transduction mechanisms. Plenum, New York, pp 189–195.
Hallam TJ, Pearson JD (1986) Exogenous ATP raises cytoplasmic free calcium in fura-2-loaded piglet aortic endothelial cells. FEBS Lett 176:139–143.
Luckhoff A, Busse, R (1986) Increased free calcium in endothelial cells under stimulation with adenine nucleotides. J Cell Physiol 126:414–420.
Pirotton S, Raspe E, Demolie D, Erneux C, Boeynaems J-M (1987) Involvement of inositol 1,4,5-trisphosphate and calcium in the action of adenine nucletides on aortic endothelial cells. J Biol Chem 262:17461–17466.
Fain JN, Wallace MA, Wojcikiewicz RJH (1988) Evidence for the involvement of guanine nucleotide-binding regulatory proteins in the activation of phospholipases by hormones. FASEB J 2:2569–2574.
Berridge MJ, Irvine RF (1989) Inositol phosphates and cell signalling. Nature 341:197–205.
Harden TK, Boyer JL, Brown HA, Cooper CL, Jeffs RA, Martin MW (1990) Biochemical properties of a P2Y-purinergic receptor. Ann NY Acad Sci 603:256–266.
Pirotton S, Erneaux C, Boeynaems J-M (1987) Dual role of GTP-binding proteins in the control of endothelial prostacyclin. Biochem Biophys Res Commun 147:1113–1120.
Brock TA, Dennis PA, Griendling KK, Diehl TS, Davies PF (1988) GTPγS loading of endothelial cells stimulates phospholipase C and uncouples ATP receptors. Am J Physiol 255:C667–C673.
Carter TD, Hallam TJ, Pearson JD (1988) Regulation of P2Y-purinoceptor-mediated prostacyclin release from human endothelial cells by cytoplasmic calcium concentration. Br J Pharmacol 94:1181–1190.
Carter TD, Newton JS, Jacob R, Pearson JD (1990) Homologous desensitization of P2Y purinoceptor-mediated elevations in cytosolic [Ca2+] and prostacyclin production in human endothelial cells does not involve protein kinase C. Biochem J 272:217–221.
Carter TD, Bogle RG, Bjaaland T (1991) Spiking of intracellular calcium ion concentration in single porcine cultured aortic endothelial cells stimulated with ATP or bradykinin. Biochem J 278:697–704.
Hallam TJ, Pearson JD, Needham LA (1988) Thrombin-stimulated elevation of human endothelial cell cytoplasmic free calcium concentration causes prostacyclin production. Biochem J 251:243–249.
Toothill VJ, Needham L, Gordon JL, Pearson JD (1988) Desensitization of agonist-stimulated prostacyclin release in human umbilical vein endothelial cells. Eur J Pharmacol 157:189–196.
Demolle D, Lecomte M, Boeynaems J-M (1988) Pattern of protein phosphorylation in aortic endothelial cells. Modulation by adenine nucleotides and bradykinin. J Biol Chem 263:18459–18465.
Kelm M, Feelisch M, Spahr R, Piper H-M, Noacke E, Schrader J (1988) Quantitative and kinetic characterization of nitric oxide and EDRF released from cultured endothelial cells. Biochem Biophys Res Commun 154:236–244.
Long CJ, Stone TW (1985) The release of endothelium-derived relaxant factor is calcium-dependent. Blood Vessels 22:205–208.
Busse R, Mulsch A (1990) Calcium-dependent nitric oxide synthesis in endothelial cytosol is mediated by calmodulin. FEBS Lett 265:133–136.
Hallam TJ, Jacob R, Merritt JE (1988) Evidence that agonists stimulate bivalent-cation influx into human endothelial cells. Biochem J 255:179–184.
Sage SO, Merritt JE, Hallam TJ, Rink TJ (1989) Receptor-mediated calcium entry in fura-2-loaded human platelets stimulated with ADP and thrombin. Biochem J 258:923–926.
Benham CD, Tsien RW (1987) A novel receptor-operated Ca2+-permeable channel activated by ATP in smooth muscle. Nature 328:275–278.
Jacob R (1990) Agonist-stimulated divalent cation entry into single cultured human umbilical vein endothelial cells. J Physiol (Lond) 421:55–77.
Lewis MJ, Henderson AH (1987) A phorbol ester inhibits the release of endothelium-derived relaxing factor. Eur J Pharmacol 137:167–171.
McCarthy SA, Hallam TJ, Merritt JE (1989) Activation of protein kinase C in human neutrophils attenuates agonist-stimulated rises in cytosolic free Ca2+ concentration by inhibiting bivalent cation influx and intracellular Ca2+ release in addition to stimulating Ca2+ efflux. Biochem J 264:352–364.
Boeynaems JM, Pearson JD (1990) P2 purinoceptors on vascular endothelial cells: Physiological significance and transduction mechanisms. Trends Pharmacol Sci 11:34–37.
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© 1991 Springer Japan
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Pearson, J.D., Carter, T.D. (1991). Endothelial Cell P2 Purinoceptors. In: Inoue, M., Hori, M., Imai, S., Berne, R.M. (eds) Regulation of Coronary Blood Flow. Springer, Tokyo. https://doi.org/10.1007/978-4-431-68367-4_16
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DOI: https://doi.org/10.1007/978-4-431-68367-4_16
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