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. 1987 May 15;244(1):93–99. doi: 10.1042/bj2440093

Prostaglandin E1 and forskolin antagonize C-kinase activation in the human platelet.

D de Chaffoy de Courcelles 1, P Roevens 1, H Van Belle 1
PMCID: PMC1147958  PMID: 2822002

Abstract

In human platelets, prostaglandin E1 and forskolin inhibit 5-hydroxytryptamine-induced phospholipase C, C-kinase and myosin light-chain kinase activity in a concentration-dependent way. Phospholipase C activation, however, was only partly inhibited, and this at higher concentrations than the protein kinases. Direct activation of the C kinase either by exogenous synthetic diacylglycerol or by 12-O-tetradecanoylphorbol 13-acetate was antagonized by prostaglandin E1 and forskolin. Since C-kinase activation is one of the key events in excitatory signal transduction in the platelets, we suggest that the inhibitory effect of agents that increase platelet cyclic AMP on platelet secretion and aggregation might reside in their capacity to antagonize C-kinase activity.

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Selected References

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  1. Adnot S., Desmier M., Ferry N., Hanoune J., Sevenet T. Forskolin (a powerful inhibitor of human platelet aggregation). Biochem Pharmacol. 1982 Dec 15;31(24):4071–4074. doi: 10.1016/0006-2952(82)90659-1. [DOI] [PubMed] [Google Scholar]
  2. Affolter H., Erne P., Bürgisser E., Pletscher A. Ca2+ as messenger of 5HT2-receptor stimulation in human blood platelets. Naunyn Schmiedebergs Arch Pharmacol. 1984 Apr;325(4):337–342. doi: 10.1007/BF00504378. [DOI] [PubMed] [Google Scholar]
  3. Baumgartner H. R., Born G. V. Effects of 5-hydroxytryptamine on platelet aggregation. Nature. 1968 Apr 13;218(5137):137–141. doi: 10.1038/218137a0. [DOI] [PubMed] [Google Scholar]
  4. Billah M. M., Lapetina E. G., Cuatrecasas P. Phosphatidylinositol-specific phospholipase-C of platelets: association with 1,2-diacyglycerol-kinase and inhibition by cyclic-AMP. Biochem Biophys Res Commun. 1979 Sep 12;90(1):92–98. doi: 10.1016/0006-291x(79)91594-8. [DOI] [PubMed] [Google Scholar]
  5. Billah M. M., Lapetina E. G. Platelet-activating factor stimulates metabolism of phosphoinositides in horse platelets: possible relationship to Ca2+ mobilization during stimulation. Proc Natl Acad Sci U S A. 1983 Feb;80(4):965–968. doi: 10.1073/pnas.80.4.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
  7. Daniel J. L., Holmsen H., Adelstein R. S. Thrombin-stimulated myosin phosphorylation in intact platelets and its possible involvement secretion. Thromb Haemost. 1977 Dec 15;38(4):984–989. [PubMed] [Google Scholar]
  8. Feinstein M. B., Egan J. J., Sha'afi R. I., White J. The cytoplasmic concentration of free calcium in platelets is controlled by stimulators of cyclic AMP production (PGD2, PGE1, forskolin). Biochem Biophys Res Commun. 1983 Jun 15;113(2):598–604. doi: 10.1016/0006-291x(83)91768-0. [DOI] [PubMed] [Google Scholar]
  9. Hallam T. J., Sanchez A., Rink T. J. Stimulus-response coupling in human platelets. Changes evoked by platelet-activating factor in cytoplasmic free calcium monitored with the fluorescent calcium indicator quin2. Biochem J. 1984 Mar 15;218(3):819–827. doi: 10.1042/bj2180819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Haslam R. J., Lynham J. A., Fox J. E. Effects of collagen, ionophore A23187 and prostaglandin E1 on the phosphorylation of specific proteins in blood platelets. Biochem J. 1979 Feb 15;178(2):397–406. doi: 10.1042/bj1780397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hatayama K., Kambayashi J., Nakamura K., Ohshiro T., Mori T. Fluorescent Ca2+-indicator quin 2 as an intracellular Ca2+ antagonist in platelet reaction. Thromb Res. 1985 Jun 1;38(5):505–512. doi: 10.1016/0049-3848(85)90183-5. [DOI] [PubMed] [Google Scholar]
  12. Imai A., Hattori H., Takahashi M., Nakashima S., Okano Y., Hattori T., Nozawa Y. Effects of dibutyryl cyclic AMP and forskolin on phospholipid biosynthesis in thrombin-stimulated human platelets. Thromb Res. 1984 Sep 1;35(5):539–546. doi: 10.1016/0049-3848(84)90285-8. [DOI] [PubMed] [Google Scholar]
  13. Kaibuchi K., Takai Y., Sawamura M., Hoshijima M., Fujikura T., Nishizuka Y. Synergistic functions of protein phosphorylation and calcium mobilization in platelet activation. J Biol Chem. 1983 Jun 10;258(11):6701–6704. [PubMed] [Google Scholar]
  14. Knight D. E., Scrutton M. C. Cyclic nucleotides control a system which regulates Ca2+ sensitivity of platelet secretion. Nature. 1984 May 3;309(5963):66–68. doi: 10.1038/309066a0. [DOI] [PubMed] [Google Scholar]
  15. Käser-Glanzmann R., Gerber E., Lüscher E. F. Regulation of the intracellular calcium level in human blood platelets: cyclic adenosine 3',5'-monophosphate dependent phosphorylation of a 22,000 dalton component in isolated Ca2+-accumulating vesicles. Biochim Biophys Acta. 1979 Dec 12;558(3):344–347. doi: 10.1016/0005-2736(79)90271-2. [DOI] [PubMed] [Google Scholar]
  16. Käser-Glanzmann R., Jakäbovä M., George J. N., Lüscher E. F. Stimulation of calcium uptake in platelet membrane vesicles by adenosine 3',5'-cyclic monophosphate and protein kinase. Biochim Biophys Acta. 1977 May 2;466(3):429–440. doi: 10.1016/0005-2736(77)90336-4. [DOI] [PubMed] [Google Scholar]
  17. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  18. Lapetina E. G., Billah M. M., Cuatrecasas P. The phosphatidylinositol cycle and the regulation of arachidonic acid production. Nature. 1981 Jul 23;292(5821):367–369. doi: 10.1038/292367a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lapetina E. G. Incorporation of synthetic 1,2-diacylglycerol into platelet phosphatidylinositol is increased by cyclic AMP. FEBS Lett. 1986 Jan 20;195(1-2):111–114. doi: 10.1016/0014-5793(86)80141-7. [DOI] [PubMed] [Google Scholar]
  20. Lapetina E. G., Siegel F. L. Shape change induced in human platelets by platelet-activating factor. Correlation with the formation of phosphatidic acid and phosphorylation of a 40,000-dalton protein. J Biol Chem. 1983 Jun 25;258(12):7241–7244. [PubMed] [Google Scholar]
  21. Lapetina E. G., Siess W. The role of phospholipase C in platelet responses. Life Sci. 1983 Sep 12;33(11):1011–1018. doi: 10.1016/0024-3205(83)90654-9. [DOI] [PubMed] [Google Scholar]
  22. Lapetina E. G., Watson S. P., Cuatrecasas P. myo-Inositol 1,4,5-trisphosphate stimulates protein phosphorylation in saponin-permeabilized human platelets. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7431–7435. doi: 10.1073/pnas.81.23.7431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lloyd J. V., Nishizawa E. E., Mustard J. F. Effect of ADP-induced shape change on incorporation of 32P into platelet phosphatidic acid and mono-, di- and triphosphatidyl inositol. Br J Haematol. 1973 Jul;25(1):77–99. doi: 10.1111/j.1365-2141.1973.tb01718.x. [DOI] [PubMed] [Google Scholar]
  24. Mills D. C., Smith J. B. The influence on platelet aggregation of drugs that affect the accumulation of adenosine 3':5'-cyclic monophosphate in platelets. Biochem J. 1971 Jan;121(2):185–196. doi: 10.1042/bj1210185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Naka M., Nishikawa M., Adelstein R. S., Hidaka H. Phorbol ester-induced activation of human platelets is associated with protein kinase C phosphorylation of myosin light chains. Nature. 1983 Dec 1;306(5942):490–492. doi: 10.1038/306490a0. [DOI] [PubMed] [Google Scholar]
  26. Nishizuka Y. Calcium, phospholipid turnover and transmembrane signalling. Philos Trans R Soc Lond B Biol Sci. 1983 Jul 5;302(1108):101–112. doi: 10.1098/rstb.1983.0043. [DOI] [PubMed] [Google Scholar]
  27. Nishizuka Y. Turnover of inositol phospholipids and signal transduction. Science. 1984 Sep 21;225(4668):1365–1370. doi: 10.1126/science.6147898. [DOI] [PubMed] [Google Scholar]
  28. Pozzan T., Arslan P., Tsien R. Y., Rink T. J. Anti-immunoglobulin, cytoplasmic free calcium, and capping in B lymphocytes. J Cell Biol. 1982 Aug;94(2):335–340. doi: 10.1083/jcb.94.2.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rao G. H., Peller J. D., Semba C. P., White J. G. Influence of the calcium-sensitive fluorophore, Quin 2, on platelet function. Blood. 1986 Feb;67(2):354–361. [PubMed] [Google Scholar]
  30. Rink T. J., Sanchez A. Effects of prostaglandin I2 and forskolin on the secretion from platelets evoked at basal concentrations of cytoplasmic free calcium by thrombin, collagen, phorbol ester and exogenous diacylglycerol. Biochem J. 1984 Sep 15;222(3):833–836. doi: 10.1042/bj2220833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rink T. J., Sanchez A., Hallam T. J. Diacylglycerol and phorbol ester stimulate secretion without raising cytoplasmic free calcium in human platelets. Nature. 1983 Sep 22;305(5932):317–319. doi: 10.1038/305317a0. [DOI] [PubMed] [Google Scholar]
  32. Rittenhouse-Simmons S. Production of diglyceride from phosphatidylinositol in activated human platelets. J Clin Invest. 1979 Apr;63(4):580–587. doi: 10.1172/JCI109339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rittenhouse S. E. Inositol lipid metabolism in the responses of stimulated platelets. Cell Calcium. 1982 Oct;3(4-5):311–322. doi: 10.1016/0143-4160(82)90019-7. [DOI] [PubMed] [Google Scholar]
  34. Siess W., Cuatrecasas P., Lapetina E. G. A role for cyclooxygenase products in the formation of phosphatidic acid in stimulated human platelets. Differential mechanisms of action of thrombin and collagen. J Biol Chem. 1983 Apr 25;258(8):4683–4686. [PubMed] [Google Scholar]
  35. Siess W., Siegel F. L., Lapetina E. G. Arachidonic acid stimulates the formation of 1,2-diacylglycerol and phosphatidic acid in human platelets. Degree of phospholipase C activation correlates with protein phosphorylation, platelet shape change, serotonin release, and aggregation. J Biol Chem. 1983 Sep 25;258(18):11236–11242. [PubMed] [Google Scholar]
  36. Simon M. F., Chap H., Douste-Blazy L. Selective inhibition of human platelet phospholipase A2 by buffering cytoplasmic calcium with the fluorescent indicator quin 2. Evidence for different calcium sensitivities of phospholipases A2 and C. Biochim Biophys Acta. 1986 Feb 12;875(2):157–164. doi: 10.1016/0005-2760(86)90164-5. [DOI] [PubMed] [Google Scholar]
  37. Tsien R. Y., Pozzan T., Rink T. J. 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. doi: 10.1083/jcb.94.2.325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Watson S. P., McConnell R. T., Lapetina E. G. The rapid formation of inositol phosphates in human platelets by thrombin is inhibited by prostacyclin. J Biol Chem. 1984 Nov 10;259(21):13199–13203. [PubMed] [Google Scholar]
  39. Watson S. P., Reep B., McConnell R. T., Lapetina E. G. Collagen stimulates [3H]inositol trisphosphate formation in indomethacin-treated human platelets. Biochem J. 1985 Mar 15;226(3):831–837. doi: 10.1042/bj2260831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wolf M., LeVine H., 3rd, May W. S., Jr, Cuatrecasas P., Sahyoun N. A model for intracellular translocation of protein kinase C involving synergism between Ca2+ and phorbol esters. Nature. 1985 Oct 10;317(6037):546–549. doi: 10.1038/317546a0. [DOI] [PubMed] [Google Scholar]
  41. Yamanishi J., Kawahara Y., Fukuzaki H. Effect of cyclic AMP on cytoplasmic free calcium in human platelets stimulated by thrombin: direct measurement with quin2. Thromb Res. 1983 Oct 15;32(2):183–188. doi: 10.1016/0049-3848(83)90029-4. [DOI] [PubMed] [Google Scholar]
  42. Zavoico G. B., Feinstein M. B. Cytoplasmic Ca2+ in platelets is controlled by cyclic AMP: antagonism between stimulators and inhibitors of adenylate cyclase. Biochem Biophys Res Commun. 1984 Apr 30;120(2):579–585. doi: 10.1016/0006-291x(84)91294-4. [DOI] [PubMed] [Google Scholar]
  43. de Chaffoy de Courcelles D. C., Roevens P., Van Belle H. R 59 022, a diacylglycerol kinase inhibitor. Its effect on diacylglycerol and thrombin-induced C kinase activation in the intact platelet. J Biol Chem. 1985 Dec 15;260(29):15762–15770. [PubMed] [Google Scholar]
  44. de Chaffoy de Courcelles D., Leysen J. E., De Clerck F., Van Belle H., Janssen P. A. Evidence that phospholipid turnover is the signal transducing system coupled to serotonin-S2 receptor sites. J Biol Chem. 1985 Jun 25;260(12):7603–7608. [PubMed] [Google Scholar]
  45. de Chaffoy de Courcelles D., Roevens P., Wynants J., Van Belle H. Serotonin-induced alterations in inositol phospholipid metabolism in human platelets. Biochim Biophys Acta. 1987 Feb 18;927(2):291–302. doi: 10.1016/0167-4889(87)90146-7. [DOI] [PubMed] [Google Scholar]
  46. de Chaffoy de Courcelles D., Roevens P., van Belle H. 12-O-Tetradecanoylphorbol 13-acetate stimulates inositol lipid phosphorylation in intact human platelets. FEBS Lett. 1984 Aug 6;173(2):389–393. doi: 10.1016/0014-5793(84)80811-x. [DOI] [PubMed] [Google Scholar]
  47. de Chaffoy de Courcelles D., Roevens P., van Belle H. Agents that elevate platelet cAMP stimulate the formation of phosphatidylinositol 4-phosphate in intact human platelets. FEBS Lett. 1986 Jan 20;195(1-2):115–118. doi: 10.1016/0014-5793(86)80142-9. [DOI] [PubMed] [Google Scholar]
  48. de Chaffoy de Courcelles D., Roevens P., van Belle H. Stimulation by serotonin of 40 kDa and 20 kDa protein phosphorylation in human platelets. FEBS Lett. 1984 Jun 11;171(2):289–292. doi: 10.1016/0014-5793(84)80506-2. [DOI] [PubMed] [Google Scholar]
  49. de Clerck F., Xhonneux B., van de Wiele R. Biochemical mechanisms in 5-hydroxytryptamine-induced human platelet aggregation. Agents Actions. 1985 Dec;17(2):220–228. doi: 10.1007/BF01966596. [DOI] [PubMed] [Google Scholar]

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