Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1984 Sep 15;222(3):833–836. doi: 10.1042/bj2220833

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.

T J Rink, A Sanchez
PMCID: PMC1144250  PMID: 6091624

Abstract

Cytoplasmic free calcium ([Ca2+]i) and secretion of ATP were measured in quin2-loaded human platelets. In certain conditions thrombin and collagen cause secretion while [Ca2+]i remains at basal concentrations, a response attributed to activation of protein kinase by diacylglycerol formed by hydrolysis of inositol lipids. This secretion evoked by thrombin could be totally suppressed by prostaglandin I2 or forskolin, as expected from the known ability of cyclic AMP to inhibit phospholipase C. The secretory response evoked by collagen at basal [Ca2+]i and that evoked by exogenous diacylglycerol or phorbol ester, direct activators of protein kinase-C, were much less affected by these inhibitors, suggesting that thrombin and collagen may promote formation of diacylglycerol by different mechanisms.

Full text

PDF

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agranoff B. W., Murthy P., Seguin E. B. Thrombin-induced phosphodiesteratic cleavage of phosphatidylinositol bisphosphate in human platelets. J Biol Chem. 1983 Feb 25;258(4):2076–2078. [PubMed] [Google Scholar]
  2. Berridge M. J. Inositol trisphosphate and diacylglycerol as second messengers. Biochem J. 1984 Jun 1;220(2):345–360. doi: 10.1042/bj2200345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. 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]
  6. Knight D. E., Hallam T. J., Scrutton M. C. Agonist selectivity and second messenger concentration in Ca2+-mediated secretion. Nature. 1982 Mar 18;296(5854):256–257. doi: 10.1038/296256a0. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Malmsten C., Granström E., Samuelsson B. Cyclic AMP inhibits synthesis of prostaglandin endoperoxide (PGG2) in human platelets. Biochem Biophys Res Commun. 1976 Jan 26;68(2):569–576. doi: 10.1016/0006-291x(76)91183-9. [DOI] [PubMed] [Google Scholar]
  9. Michell R. H. Stimulated inositol lipid metabolism: an introduction. Cell Calcium. 1982 Oct;3(4-5):285–294. doi: 10.1016/0143-4160(82)90017-3. [DOI] [PubMed] [Google Scholar]
  10. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Rink T. J., Smith S. W., Tsien R. Y. Cytoplasmic free Ca2+ in human platelets: Ca2+ thresholds and Ca-independent activation for shape-change and secretion. FEBS Lett. 1982 Nov 1;148(1):21–26. doi: 10.1016/0014-5793(82)81234-9. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Siegl A. M., Daly J. W., Smith J. B. Inhibition of aggregation and stimulation of cyclic AMP generation in intact human platelets by the diterpene forskolin. Mol Pharmacol. 1982 May;21(3):680–687. [PubMed] [Google Scholar]
  15. Streb H., Irvine R. F., Berridge M. J., Schulz I. Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate. Nature. 1983 Nov 3;306(5938):67–69. doi: 10.1038/306067a0. [DOI] [PubMed] [Google Scholar]
  16. 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]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES