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. 1985 Nov 15;232(1):61–66. doi: 10.1042/bj2320061

Decanoyl lysophosphatidic acid induces platelet aggregation through an extracellular action. Evidence against a second messenger role for lysophosphatidic acid.

S P Watson, R T McConnell, E G Lapetina
PMCID: PMC1152839  PMID: 3853461

Abstract

Platelets rapidly convert 1,2-didecanoyl-sn-glycerol into its corresponding phosphatidic acid and lysophosphatidic acid derivatives, thereby providing a means of introducing these two compounds into platelets. 1-Decanoyl-2-lyso-3-sn-phosphatidic acid, when added directly to platelets, induced platelet aggregation and raised intracellular Ca2+ levels at concentrations of 0.3 microM upwards, but was without effect when formed intracellularly from 1,2-didecanoylglycerol at an estimated concentration of approx. 47 microM. This indicates that the site of platelet activation by lysophosphatidic acid is extracellular. A concentration of thrombin (0.2 unit/ml), which produced maximal platelet aggregation, caused an estimated intracellular formation of 20 microM-lysophosphatidic acid in the presence of 2 mM-Ca2+; however, there was no detectable release of lysophosphatidic acid into the bathing medium. Lysophosphatidic acid, therefore, may not be an intracellular second messenger involved in platelet aggregation by thrombin.

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Selected References

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  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. Apitz-Castro R., Cruz M., Mas M., Jain M. K. Further studies on a phospholipase A2 isolated from human platelet plasma membranes. 1981 Aug 15-Sep 1Thromb Res. 23(4-5):347–354. doi: 10.1016/0049-3848(81)90195-x. [DOI] [PubMed] [Google Scholar]
  3. Bell R. L., Kennerly D. A., Stanford N., Majerus P. W. Diglyceride lipase: a pathway for arachidonate release from human platelets. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3238–3241. doi: 10.1073/pnas.76.7.3238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benton A. M., Gerrard J. M., Michiel T., Kindom S. E. Are lysophosphatidic acids or phosphatidic acids involved in stimulus activation coupling in platelets? Blood. 1982 Sep;60(3):642–649. [PubMed] [Google Scholar]
  5. Berridge M. J., Downes C. P., Hanley M. R. Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands. Biochem J. 1982 Sep 15;206(3):587–595. doi: 10.1042/bj2060587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  7. Billah M. M., Lapetina E. G., Cuatrecasas P. Phospholipase A2 activity specific for phosphatidic acid. A possible mechanism for the production of arachidonic acid in platelets. J Biol Chem. 1981 Jun 10;256(11):5399–5403. [PubMed] [Google Scholar]
  8. Billah M. M., Lapetina E. G. Rapid decrease of phosphatidylinositol 4,5-bisphosphate in thrombin-stimulated platelets. J Biol Chem. 1982 Nov 10;257(21):12705–12708. [PubMed] [Google Scholar]
  9. Broekman M. J., Ward J. W., Marcus A. J. Phospholipid metabolism in stimulated human platelets. Changes in phosphatidylinositol, phosphatidic acid, and lysophospholipids. J Clin Invest. 1980 Aug;66(2):275–283. doi: 10.1172/JCI109854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cohen P., Derksen A. Comparison of phospholipid and fatty acid composition of human erythrocytes and platelets. Br J Haematol. 1969 Oct;17(4):359–371. doi: 10.1111/j.1365-2141.1969.tb01382.x. [DOI] [PubMed] [Google Scholar]
  11. Gerrard J. M., Butler A. M., Peterson D. A., White J. G. Phosphatidic acid releases calcium from a platelet membrane fraction in vitro. Prostaglandins Med. 1978 Nov;1(5):387–396. doi: 10.1016/0161-4630(78)90125-8. [DOI] [PubMed] [Google Scholar]
  12. Gerrard J. M., Kindom S. E., Peterson D. A., Peller J., Krantz K. E., White J. G. Lysophosphatidic acids. Influence on platelet aggregation and intracellular calcium flux. Am J Pathol. 1979 Aug;96(2):423–438. [PMC free article] [PubMed] [Google Scholar]
  13. Gerrard J. M., Robinson P. Lysophosphatidic acid can activate platelets without increasing 32P-labelling of phosphatidic acid. Biochim Biophys Acta. 1984 Oct 4;795(3):487–492. doi: 10.1016/0005-2760(84)90177-2. [DOI] [PubMed] [Google Scholar]
  14. Hallam T. J., Scrutton M. C., Wallis R. B. The role of 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (AcGEPC) and palmitoyl-lysophosphatidate in the responses of human blood platelets to collagen and thrombin. FEBS Lett. 1983 Oct 3;162(1):142–146. doi: 10.1016/0014-5793(83)81066-7. [DOI] [PubMed] [Google Scholar]
  15. Holmes R. P., Yoss N. L. Failure of phosphatidic acid to translocate Ca2+ across phosphatidylcholine membranes. Nature. 1983 Oct 13;305(5935):637–638. doi: 10.1038/305637a0. [DOI] [PubMed] [Google Scholar]
  16. Holmsen H., Dangelmaier C. A., Rongved S. Tight coupling of thrombin-induced acid hydrolase secretion and phosphatidate synthesis to receptor occupancy in human platelets. Biochem J. 1984 Aug 15;222(1):157–167. doi: 10.1042/bj2220157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Lapetina E. G., Billah M. M., Cuatrecasas P. Lysophosphatidic acid potentiates the thrombin-induced production of arachidonate metabolites in platelets. J Biol Chem. 1981 Dec 10;256(23):11984–11987. [PubMed] [Google Scholar]
  19. 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]
  20. Lapetina E. G. Prostacyclin inhibition of phosphatidic acid synthesis in human platelets is not mediated by protein kinase C. Biochem Biophys Res Commun. 1984 Apr 16;120(1):37–44. doi: 10.1016/0006-291x(84)91410-4. [DOI] [PubMed] [Google Scholar]
  21. MacIntyre D. E., Shaw A. M. Phospholipid-induced human platelet activation: effects of calcium channel blockers and calcium chelators. Thromb Res. 1983 Sep 15;31(6):833–844. doi: 10.1016/0049-3848(83)90114-7. [DOI] [PubMed] [Google Scholar]
  22. Mauco G., Chap H., Simon M. F., Douste-Blazy L. Phosphatidic and lysophosphatidic acid production in phospholipase C-and thrombin-treated platelets. Possible involvement of a platelet lipase. Biochimie. 1978 Sep 29;60(6-7):653–661. doi: 10.1016/s0300-9084(78)80784-6. [DOI] [PubMed] [Google Scholar]
  23. Nayar R., Mayer L. D., Hope M. J., Cullis P. R. Phosphatidic acid as a calcium ionophore in large unilamellar vesicle systems. Biochim Biophys Acta. 1984 Nov 7;777(2):343–346. doi: 10.1016/0005-2736(84)90438-3. [DOI] [PubMed] [Google Scholar]
  24. O'Rourke F. A., Halenda S. P., Zavoico G. B., Feinstein M. B. Inositol 1,4,5-trisphosphate releases Ca2+ from a Ca2+-transporting membrane vesicle fraction derived from human platelets. J Biol Chem. 1985 Jan 25;260(2):956–962. [PubMed] [Google Scholar]
  25. Putney J. W., Jr Recent hypotheses regarding the phosphatidylinositol effect. Life Sci. 1981 Sep 21;29(12):1183–1194. doi: 10.1016/0024-3205(81)90221-6. [DOI] [PubMed] [Google Scholar]
  26. Putney J. W., Jr, Weiss S. J., Van De Walle C. M., Haddas R. A. Is phosphatidic acid a calcium ionophore under neurohumoral control? Nature. 1980 Mar 27;284(5754):345–347. doi: 10.1038/284345a0. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. 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]
  29. Salmon D. M., Honeyman T. W. Proposed mechanism of cholinergic action in smooth muscle. Nature. 1980 Mar 27;284(5754):344–345. doi: 10.1038/284344a0. [DOI] [PubMed] [Google Scholar]
  30. Serhan C., Anderson P., Goodman E., Dunham P., Weissmann G. Phosphatidate and oxidized fatty acids are calcium ionophores. Studies employing arsenazo III in liposomes. J Biol Chem. 1981 Mar 25;256(6):2736–2741. [PubMed] [Google Scholar]
  31. 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]
  32. Simon M. F., Chap H., Douste-Blazy L. Platelet aggregating activity of lysophosphatidic acids is not related to their calcium ionophore properties. FEBS Lett. 1984 Jan 23;166(1):115–119. doi: 10.1016/0014-5793(84)80055-1. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Tokumura A., Fukuzawa K., Isobe J., Tsukatani H. Lysophosphatidic acid-induced aggregation of human and feline platelets: structure-activity relationship. Biochem Biophys Res Commun. 1981 Mar 31;99(2):391–398. doi: 10.1016/0006-291x(81)91758-7. [DOI] [PubMed] [Google Scholar]
  35. Tokumura A., Fukuzawa K., Yamada S., Tsukatani H. Stimulatory effect of lysophosphatidic acids on uterine smooth muscles of non-pregant rats. Arch Int Pharmacodyn Ther. 1980 May;245(1):74–83. [PubMed] [Google Scholar]
  36. Tsien R. Y., Pozzan T., Rink T. J. T-cell mitogens cause early changes in cytoplasmic free Ca2+ and membrane potential in lymphocytes. Nature. 1982 Jan 7;295(5844):68–71. doi: 10.1038/295068a0. [DOI] [PubMed] [Google Scholar]
  37. Tyson C. A., Vande Zande H., Green D. E. Phospholipids as ionophores. J Biol Chem. 1976 Mar 10;251(5):1326–1332. [PubMed] [Google Scholar]
  38. VOGT W. Pharamacologically active acidic phospholipids and glycolipids. Biochem Pharmacol. 1963 Apr;12:415–420. doi: 10.1016/0006-2952(63)90074-1. [DOI] [PubMed] [Google Scholar]
  39. Vaskovsky V. E., Latyshev N. A. Modified Jungnickel's reagent for detecting phospholipids and other phosphorus compounds on thin-layer chromatograms. J Chromatogr. 1975 Dec 10;115(1):246–249. doi: 10.1016/s0021-9673(00)89042-1. [DOI] [PubMed] [Google Scholar]
  40. Watson S. P., Ganong B. R., Bell R. M., Lapetina E. G. 1,2-Diacylglycerols do not potentiate the action of phospholipases A2 and C in human platelets. Biochem Biophys Res Commun. 1984 May 31;121(1):386–391. doi: 10.1016/0006-291x(84)90734-4. [DOI] [PubMed] [Google Scholar]
  41. 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]
  42. 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]

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