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Endothelial Cell P2 Purinoceptors

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Regulation of Coronary Blood Flow

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

  1. 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.

    Google Scholar 

  2. Gordon JL (1986) Extracellular ATP: Effects, sources and fate. Biochem J 233:309–319.

    PubMed  CAS  Google Scholar 

  3. Pearson JD, Gordon JL (1979) Vascular endothelial and smooth muscle cells in culture selectively release adenine nucleotides. Nature 281:384–386.

    Article  PubMed  CAS  Google Scholar 

  4. 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.

    Article  Google Scholar 

  5. Olsson R, Pearson JD (1990) Cardiovascular purinoceptors. Physiol Rev 70:761–845.

    PubMed  CAS  Google Scholar 

  6. Pearson JD, Gordon JL (1985) Nucleotide metabolism by endothelium. Ann Rev Physiol 47:617–627.

    Article  CAS  Google Scholar 

  7. 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.

    Chapter  Google Scholar 

  8. Winbury MM, Papierski DH, Hemmer ML, Hambourger WE (1953) Coronary dilator action of the adenine-ATP series. J Pharmacol Exp Ther 109:255–260.

    PubMed  CAS  Google Scholar 

  9. 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.

    Chapter  Google Scholar 

  10. 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.

    Google Scholar 

  11. Furchgott RF (1984) The role of the endothelium in the responses of vascluar smooth muscle to drugs. Annu Rev Pharmacol Toxicol 24:175–197.

    Article  PubMed  CAS  Google Scholar 

  12. Palmer RMJ, Ashton DS, Moncada S (1988) Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333:664–666.

    Article  PubMed  CAS  Google Scholar 

  13. 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.

    Article  PubMed  CAS  Google Scholar 

  14. Burnstock G, Kennedy C (1985) Is there a basis for distinguishing two types of P2-purinoceptor? Gen Pharmacol 16:433–440.

    Article  PubMed  CAS  Google Scholar 

  15. Pearson JD, Slakey LL, Gordon JL (1983) Stimulation of prostacyclin production through purinoceptors on cultured porcine aortic endothelial cells. Biochem J 214:273–276.

    PubMed  CAS  Google Scholar 

  16. 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.

    Chapter  Google Scholar 

  17. Hallam TJ, Pearson JD (1986) Exogenous ATP raises cytoplasmic free calcium in fura-2-loaded piglet aortic endothelial cells. FEBS Lett 176:139–143.

    Google Scholar 

  18. Luckhoff A, Busse, R (1986) Increased free calcium in endothelial cells under stimulation with adenine nucleotides. J Cell Physiol 126:414–420.

    Article  PubMed  CAS  Google Scholar 

  19. 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.

    PubMed  CAS  Google Scholar 

  20. 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.

    PubMed  CAS  Google Scholar 

  21. Berridge MJ, Irvine RF (1989) Inositol phosphates and cell signalling. Nature 341:197–205.

    Article  PubMed  CAS  Google Scholar 

  22. 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.

    Article  PubMed  CAS  Google Scholar 

  23. 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.

    Article  PubMed  CAS  Google Scholar 

  24. 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.

    PubMed  CAS  Google Scholar 

  25. 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.

    Article  Google Scholar 

  26. 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.

    PubMed  CAS  Google Scholar 

  27. 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.

    PubMed  CAS  Google Scholar 

  28. 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.

    PubMed  CAS  Google Scholar 

  29. 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.

    Article  PubMed  CAS  Google Scholar 

  30. 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.

    PubMed  CAS  Google Scholar 

  31. 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.

    Article  PubMed  CAS  Google Scholar 

  32. Long CJ, Stone TW (1985) The release of endothelium-derived relaxant factor is calcium-dependent. Blood Vessels 22:205–208.

    PubMed  CAS  Google Scholar 

  33. Busse R, Mulsch A (1990) Calcium-dependent nitric oxide synthesis in endothelial cytosol is mediated by calmodulin. FEBS Lett 265:133–136.

    Article  PubMed  CAS  Google Scholar 

  34. Hallam TJ, Jacob R, Merritt JE (1988) Evidence that agonists stimulate bivalent-cation influx into human endothelial cells. Biochem J 255:179–184.

    PubMed  CAS  Google Scholar 

  35. 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.

    PubMed  CAS  Google Scholar 

  36. Benham CD, Tsien RW (1987) A novel receptor-operated Ca2+-permeable channel activated by ATP in smooth muscle. Nature 328:275–278.

    Article  PubMed  CAS  Google Scholar 

  37. Jacob R (1990) Agonist-stimulated divalent cation entry into single cultured human umbilical vein endothelial cells. J Physiol (Lond) 421:55–77.

    CAS  Google Scholar 

  38. Lewis MJ, Henderson AH (1987) A phorbol ester inhibits the release of endothelium-derived relaxing factor. Eur J Pharmacol 137:167–171.

    Article  PubMed  CAS  Google Scholar 

  39. 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.

    Google Scholar 

  40. Boeynaems JM, Pearson JD (1990) P2 purinoceptors on vascular endothelial cells: Physiological significance and transduction mechanisms. Trends Pharmacol Sci 11:34–37.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Section of Vascular Biology, Clinical Research Centre, Harrow, HA1 3UJ, UK

    Jeremy D. Pearson

  2. Divison of Neurophysiology and Neuropharmacology, National Institute for Medical Research, Mill Hill, London, UK

    Thomas D. Carter

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  1. Jeremy D. Pearson
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  2. Thomas D. Carter
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Editor information

Editors and Affiliations

  1. Department of Medical Information Sciences, Osaka University Hospital, Osaka, 553, Japan

    Michitoshi Inoue M.D., Ph.D. (Professor) (Professor)

  2. The First Department of Medicine, Osaka University School of Medicine, Osaka, 553, Japan

    Masatsugu Hori M.D., Ph.D. (Assistant Professor) (Assistant Professor)

  3. Department of Pharmacology, Niigata University School of Medicine, Niigata, 951, Japan

    Shoichi Imai M.D., Ph.D. (Professor) (Professor)

  4. Department of Physiology, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA

    Robert M. Berne M.D. (Alumni Professor) (Alumni Professor)

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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

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-68369-8

  • Online ISBN: 978-4-431-68367-4

  • eBook Packages: Springer Book Archive

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