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The human platelet 5-HT2-receptor: an up-date

  • D. de Chaffoy de Courcelles
  • F. de Clerck
Chapter
Part of the Developments in CardioCardiovascular Pharmacology of 5-Hydroxytryptamine book series (DICM, volume 106)

Abstract

Platelets are oval discs 2 to 3 μm in diameter, circulating in the blood. They can adhere to damaged blood vessel walls (adhesion) and stick to each other (aggregation). Platelets contain α -granules, dense bodies, lysosomes, mitochondria and glycogen particles. Three different channel-like structures have been identified: an open canalicular system, a dense tubular system and circumferential microtubules. The platelet plasma membrane resembles, in structure as well as in function, that of cells of other tissue. In the sub-membrane area, platelets have microtubules which support their discoid shape and microfilaments which contain contractile proteins involved in the platelet release reaction. Such a release reaction is provoked by platelet stimulation with excitatory agonists. This results in the appearance in the extracellular space of the content of the granules, the dense bodies and the lysosome-like particles. The α -granules contain secretable platelet proteins, such as fibrinogen, β - thromboglobulin, platelet factor-4 and cationic proteins. The dense bodies mainly contain ATP, ADP, calcium and serotonin. The lysosome-like particles contain acid hydrolases. The extent of secretion of the contents of these different subcellular particles depends upon the nature and the concentration of the challenging agonist. Platelets also biosynthetize and release metabolites from arachidonic acid (see also section 1.2).

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References

  1. 1.
    Holmsen H (1977): Prostaglandin endoperoxide-thromboxane synthesis and dense granule secretion as positive feedback loops in the propagation of platelet responses during “the basic platelet reaction”.Thromb Haemost 38: 1030–1041.PubMedGoogle Scholar
  2. 2.
    Vargaftig BB, Chignard M, Benveniste J (1981): Present concepts on mechanisms of platelet aggregation. Biochem Pharmacol 30: 263–271.PubMedCrossRefGoogle Scholar
  3. 3.
    Zucker MB, Nachmias VT (1985): Platelet activation. Arteriosclerosis 5: 2–18.PubMedCrossRefGoogle Scholar
  4. 4.
    Lapetina E (1987): Inositide-dependent and independent mechanisms in platelets activation, pp. 287–310 in: Putney Jr. JW(ed), Phosphoinositides and receptor mechanisms . New York: Alan R. Liss, Inc.Google Scholar
  5. 5.
    Nishizuka Y (1984): Turnover of inositol phospholipids and signal transduction. Science 225: 1365–1370.PubMedCrossRefGoogle Scholar
  6. 6.
    O’Rourke FA, Halenda SP, Zavoico GB, Feinstein MB (1985): Inositol 1,4,5-trisphosphate releases Ca2+ from a Ca2+-transporting membrane vesicle fraction derived from human platelets. J Biol Chem 260: 956–962.PubMedGoogle Scholar
  7. 7.
    Authi KS, Crawford N (1985): Inositol 1,4,5-trisphosphate-induced release of sequestered Ca2+ from highly purified human platelet intracellular membranes. Biochem J 230: 247–253.PubMedGoogle Scholar
  8. 8.
    Sage SO, Rink TJ (1987): The kinetics of changes in intracellular calcium concentration in fura-2-loaded human platelets. J Biol Chem 262: 16364–16369PubMedGoogle Scholar
  9. 9.
    Sage SO, Rink TJ (1986): Kinetic differences between thrombin- induced and ADP-induced calcium influx and release from internal stores in fura-2-loaded human platelets. Biochem Biophys Res Commun 136: 1124–1129.PubMedCrossRefGoogle Scholar
  10. 10.
    Hallam TJ, Rink TJ (1985): Agonists stimulate divalent cation channels in the plasma membrane of human platelets. FEBS 186: 175–179.CrossRefGoogle Scholar
  11. 11.
    Sage SO, Rink TJ (1986): Effects of ionic substitution on [Ca2+]i rises evoked by thrombin and PAF in human platelets. Eur J Pharmacol 128: 99–107.PubMedCrossRefGoogle Scholar
  12. 12.
    Sage SO, Rink TJ (1986): Effects of ionic substitution on [Ca2+]i rises evoked by thrombin and PAF in human platelets. Eur J Pharmacol 128: 99–107.PubMedCrossRefGoogle Scholar
  13. 13.
    Kaibuchi K, Takai Y, Sawamura M, Hoshijima M, Fujikura T and Nishizuka Y (1983): Synergistic functions of protein phosphorylation and calcium mobilization in platelet activation. JBiol Chem 258: 670–6704.Google Scholar
  14. 14.
    Rink TJ, Sanchez A, Hallam TJ (1983): Diacylglycerol and phorbol ester stimulate secretion without raising cytoplasmic free calcium in human platelets. Nature 305: 317–319.PubMedCrossRefGoogle Scholar
  15. 15.
    Maclntyre DE, McNicol A, Drummond AH (1985): Tumour-promoting phorbol esters inhibit agonist-induced phosphatidate formation and Ca2+ flux in human platelets. FEBS 180: 160–164.CrossRefGoogle Scholar
  16. 16.
    Watson SP, Lapetina EG (1985): 1,2-Diacylglycerol and phorbol ester inhibit agonist- induced formation of inositol phosphates in human platelets: possible implications for negative feedback regulation of inositol phospholipid hydrolysis. Proc Natl Acad Sci USA 82:2623–2626.PubMedCrossRefGoogle Scholar
  17. 17.
    Pollock WK, Sage SO, Rink TJ (1987): Stimulation of Ca2+ efflux from fura-2-loaded platelets activated by thrombin or phorbol myristate acetate. FEBS 210: 132–136.CrossRefGoogle Scholar
  18. 18.
    Rink TJ, Sage SO (1987): Stimulated calcium efflux from fura-2-loaded human platelets. J Physiol 393: 513–524.PubMedGoogle Scholar
  19. 19.
    Wilson DB, Neufeld EJ, Majerus PW (1985): Phosphoinositide interconversion in thrombin-stimulated human platelets. J Biol Chem 260: 1046–1051.PubMedGoogle Scholar
  20. 20.
    Siess W, Cuatrecasas P, Lapetina EG (1983): A role for cyclooxygenase products in the formation of phosphatidic acid in stimulated human platelets. J Biol Chem 258: 4683–4686.PubMedGoogle Scholar
  21. 21.
    Billah MM, Lapetina EG, Cuatrecasas P (1980): Phospholipase A2 and phospholipase C activities of platelets. Differential substrate specificity, Ca2+ requirements, pH dependency and cellular localization. J Biol Chem 255: 10227–10231.PubMedGoogle Scholar
  22. 22.
    Gerrard JM, Peterson DA, White JG (1981): Calcium mobilization, pp. 407–436 in: Gordon JL (ed), Platelets in biology and pathology-2 . Amsterdam: Biomedical Press.Google Scholar
  23. 23.
    Maclntyre DE (1981): Platelet prostaglandin receptors, pp. 211–248 in Gordon JL (ed), Platelets in biology and pathology-2 . Amsterdam: Biomedical Press.Google Scholar
  24. 24.
    Chan KM, Turk J (1987): Mechanism of arachidonic acid-induced Ca2+ mobilization from rat liver microsomes. Biochim Biophys Acta 928: 186–193.PubMedCrossRefGoogle Scholar
  25. 25.
    Wolf BA, Turk J, Sherman WR, McDaniel ML (1986): Intracellular Ca2+ mobilization by arachidonic acid. J Biol Chem 261: 3501–3511.PubMedGoogle Scholar
  26. 26.
    Nishikawa M, Hidaka H, Shirakawa S (1988): Possible involvement of direct stimulation of protein kinase C by unsaturated fatty acids in platelet activation. Biochem Pharmacol 37: 3079–3089.PubMedCrossRefGoogle Scholar
  27. 27.
    Sekiguchi K, Tsukuda M, Ogita K, Kikkawa U, Nishizuka Y (1987): Three distinct forms of rat brain protein kinase C: differential response to unsaturated fatty acids. Biochem Biophys Res Commun 145: 797–802.PubMedCrossRefGoogle Scholar
  28. 28.
    Daniel JL, Dangelmaier CA, Selak M, Smith JB (1986): ADP stimulates IP3 formation in human platelets. FEBS 206:299–303.CrossRefGoogle Scholar
  29. 29.
    Fisher GJ, Bakshian S, Baldassare JJ (1985): Activation of human platelets by ADP causes a rapid rise in cytosolic free calcium without hydrolysis of phosphatidylinositol-4,5- bisphosphate. Biochem Biophys Res Commun 129:958–964.PubMedCrossRefGoogle Scholar
  30. 30.
    Figures WR, Scearce LM, Wachtfogel Y, Chen J, Colman RF and Colman RW (1986): Platelet ADP receptor and α2-adrenoreceptor interaction. J Biol Chem 261: 5981–5986.PubMedGoogle Scholar
  31. 31.
    Siess W, Weber PC (1984): Activation of phospholipase C is dissociated from arachidonate metabolism during platelet shape change induced by thrombin or platelet- activating factor. J Biol Chem 259: 8286–8292.PubMedGoogle Scholar
  32. 32.
    Vanderwel M, Lum DS, Haslam RJ (1983); Vasopressin inhibits the adenylate cyclase activity of human platelet particulate fraction through V1-receptors. FEBS Lett 164: 340–344.PubMedCrossRefGoogle Scholar
  33. 33.
    Williams KA, Haslam RJ (1984): Effects of NaCl and GTP on the inhibition of platelet adenylate cyclase by l–0-octadecyl-2–0-acetyl-sn-glyceryl-3-phosphorylcholine (synthetic platelet-activating factor). Biochim Biophys Acta 770: 216–223.PubMedCrossRefGoogle Scholar
  34. 34.
    Avdonin PV, Svitina-Ulitina IV, Letin VL, Tkachuk VA (1985): Interaction of stable prostaglandin endoperoxide analogs U46619 and U44069 with human platelet membranes: coupling of receptors with high-affinity GTPase and adenylate cyclase. Thromb Res 40: 101–112, 1985.PubMedCrossRefGoogle Scholar
  35. 35.
    Williams KA, Murphy W, Haslam RJ (1987): Effects of activation of protein kinase C on the agonist-induced stimulation and inhibition of cyclic AMP formation in intact human platelets. Biochem J 243: 667–678.PubMedGoogle Scholar
  36. 36.
    De Clerck F (1988): Human platelet aggregation induced by 5-hydroxytryptamine: a methodological study. Hematol Rev 2: 197–262.Google Scholar
  37. 37.
    Michal F, Penglis F (1969): Inhibition of serotonin-induced platelet aggregation in relation to thrombus production. J Pharmacol Exp Ther 166: 276–284.PubMedGoogle Scholar
  38. 38.
    Drummond AH, Gordon JL (1974): Platelet release reaction induced by 5-hydroxy- tryptamine. J Physiol 240:39P–40P.Google Scholar
  39. 39.
    Gordon JL, Drummond AH (1975): Irreversible aggregation of pig platelets and release of intracellular constituents induced by 5-hydroxytryptamines. Biochem Pharmacol 24: 33–6.PubMedCrossRefGoogle Scholar
  40. 40.
    de Chaffoy de Courcelles D, Roevens P, Van Belle H (1984): Stimulation by serotonin of 40 kDa and 20 kDa protein phosphorylation in human platelets. FEBS 171: 289–292.CrossRefGoogle Scholar
  41. 41.
    de Chaffoy de Courcelles D, Leysen JE, De Clerck F, Van Belle H, Janssen PAJ (1985): Evidence that phospholipid turnover is the signal transducing system coupled to serotonin-S2 receptor sites. J Biol Chem 260: 7603–7608.PubMedGoogle Scholar
  42. 42.
    de Chaffoy de Courcelles D, Roevens P, Van Belle H, De Clerck F (1987): The synergistic effect of serotonin and epinephrine on the human platelet at the level of signal transduction. FEBS 219: 283–288.CrossRefGoogle Scholar
  43. 43.
    de Chaffoy de Courcelles D, Roevens P, Wynants J, Van Belle H (1987): Serotonin- induced alterations in inositol phospholipid metabolism in human platelets. Biochim Biophys Acta 927: 291–302.PubMedCrossRefGoogle Scholar
  44. 44.
    Cabot MC, Welsh CJ, Zhang Z, Cao H, Chabbott H, Lebowitz M (1988): Vasopressin, phorbol diesters and serum elicit choline glycerophospholipid hydrolysis and diacylglycerol formation in nontransformed cells: transformed derivatives do not respond. Biochim Biophys Acta 959: 46–57.PubMedCrossRefGoogle Scholar
  45. 45.
    Irving HR, Exton JH (1987): Phosphatidylcholine breakdown in rat liver plasma membranes. J Biol Chem 262: 3440–3443.PubMedGoogle Scholar
  46. 46.
    de Chaffoy de Courcelles D (In press): Is there evidence for a role of the phospho-inositol-cycle in the myocardium?Google Scholar
  47. 47.
    De Clerck F, Herman AG (1983). 5-Hydroxytryptamine and platelet aggregation. Fed Proc 42:228–232.PubMedGoogle Scholar
  48. 48.
    De Clerck F, Van Nueten JM, Reneman RS (1984): Platelet-vessel wall interactions: implication of 5-hydroxytryptamine. A review. Agents Actions 15: 612–626.PubMedCrossRefGoogle Scholar
  49. 49.
    De Clerck F, Xhonneux B, Leysen J, Janssen PAJ (1984): Evidence for functional 5-HT receptor sites on human blood platelets. Biochem Pharmacol 33: 2807–2811.PubMedCrossRefGoogle Scholar
  50. 50.
    Ardlie NG, Cameron HA, Garrat J (1984): Platelet activation by circulating levels of hormones: a possible link in coronary heart disease. Thromb Res 36: 315–322.PubMedCrossRefGoogle Scholar
  51. 51.
    Baumgartner HR, Born GVR (1968): Effects of 5-hydroxytryptamine on platelet aggregation. Nature 218: 137–141.PubMedCrossRefGoogle Scholar
  52. 52.
    De Clerck F, David JL, Janssen PAJ (1982): Inhibition of 5- hydroxytryptamine-induced and -amplified human platelet aggregation by ketanserin (R 41 468), a selective 5-HT2- receptor antagonist. Agents Actions 12: 388–397.PubMedCrossRefGoogle Scholar
  53. 53.
    Grant JA, Scrutton MC (1980): Positive interaction between agonists in the aggregation response of human blood platelets: interaction between ADP, adrenaline and vasopressin. Br J Haematol 44: 109–125.PubMedCrossRefGoogle Scholar
  54. 54.
    Huang EM, Detweiler TC (1981): Characteristics of the synergistic actions of platelet agonists. Blood 57: 685 – 691.PubMedGoogle Scholar
  55. 55.
    Nakanishi M, Imamura H, Goto K (1971): Potentiation of ADP-induced platelet aggregation by collagen and its inhibition by a tetrahydrotheino-pyridine derivative. Biochem Pharmacol 20: 2116–2118.PubMedCrossRefGoogle Scholar
  56. 56.
    Kinlough-Rathbone RL, Packham MA, Mustard JF (1977): Synergism between platelet aggregating agents: the role of the arachidonate pathway. Thromb Res 11: 567–580.PubMedCrossRefGoogle Scholar
  57. 57.
    Silver MJ, Smith JB, Ingerman L, Kolsis JJ (1973): Arachidonic acid-induced human platelet aggregation and prostaglandin formation. Prostaglandins 4: 863–876.PubMedCrossRefGoogle Scholar
  58. 58.
    Bushfield M, Lumley P, Maclntyre De (1986): Synergistic activation of human platelets in whole blood. Br J Pharmacol 89: 855 P.Google Scholar
  59. 59.
    De Clerck F, Somers Y, Van Gorp L (1984): Platelet-vessel wall interactions in haemostasis: implication of 5-hydroxytryptamine. Agents Actions 15: 627–635.PubMedCrossRefGoogle Scholar
  60. 60.
    Setiabudy-Dharma R, Funahara, Y (1986): Enhancement of collagen-induced aggregation of platelets in whole blood. Thromb Res 48: 621–634.CrossRefGoogle Scholar
  61. 61.
    Doni MG, Aragno R (1977): Effect of catecholamine on ADP aggregation of rat platelets in vivo. Experientia 33: 1331–1332.PubMedCrossRefGoogle Scholar
  62. 62.
    Holmes IB (1979): Potentiating effect of adrenaline on adenosine diphosphate- induced reduction in rabbit circulating platelet count: inhibition by dihydroergotamine. Thromb Haemost 42: 641–648.PubMedGoogle Scholar
  63. 63.
    Van Nueten JM, Janssen PAJ, Symoens J, Janssens WJ, Heykants J, De Clerck F, Leysen JE, Van Cauteren H, Vanhoutte PM (1987): Ketanserin, pp. 1–56 in: Scriabine A (ed), New cardiovascular drugs . New York: Raven Press.Google Scholar
  64. 64.
    De Clerck F, Xhonneux B, de Chaffoy de Courcelles D. (1988): Functional expression of the amplification reaction between serotonin and epinephrine on platelets. J Cardiovasc Pharmacol 11 (Suppl. 1): S1–S5.Google Scholar
  65. 65.
    Michal F, Motamed M (1976): Shape change and aggregation of blood platelets: interaction between the effect of adenosine diphosphate, 5-hydroxytryptamine and adrenaline. Br J Pharmacol 56: 209–218.PubMedCrossRefGoogle Scholar
  66. 66.
    de Chaffoy de Courcelles D, Roevens P, De Clerck F (1988): The synergistic effect of serotonin and epinephrine at the level of signal transduction. J Cardiovasc Pharmacol 11 (Suppl. 1): S107–S110.CrossRefGoogle Scholar
  67. 67.
    De Clerck F, de Chaffoy de Courcelles D (1987): Amplification mechanisms in platelet activation, in: Meyer F, Marche P (eds), Blood cells and arteries in hypertension and atherosclerosis . New York: Raven Press.Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1990

Authors and Affiliations

  • D. de Chaffoy de Courcelles
  • F. de Clerck

There are no affiliations available

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