An activation mechanism of platelet phospholipases

  • Reiji Kannagi


Prostaglandins and thromboxanes have been implicated with platelet function (see Samuelsson et al. 1978 for review). Since the converting enzyme in their synthesis is highly active in platelets, its efficiency is considered to be limited by the availability of substrate, arachidonate. Because of this, the release of arachidonate from phospholipids by phospholipases has been regarded as the rate limiting step in the synthesis of prostaglandins and thromboxanes. Many cells and tissues can release arachidonate in response to stimulation, and platelets serve as the most fitted experimental system for study of this phospholipase reaction. Since arachidonate is esterified almost exclusively at the sn-2-position of glycerol of phospholipids in platelets, it had been generally assumed that activation of the enzyme having an A2 specificity is responsible for the release of arachidonate. However, free arachidonate can be released not only by phospholipase A2 alone, but also by the combined action of either phospholipase A1 plus lysophospholipase, or phospholipase C plus DG and MG lipases. Plasmalogenases could also participate in the reaction. It has been rather difficult to elucidate the exact pathway of arachidonate release by studying arachidonate release from the endogenous phospholipid pool of intact platelets, and the detailed enzymological study to test these various possible pathways has not been started until recently.


Human Platelet Phosphatidic Acid Platelet Membrane Glyceryl Ether Rabbit Platelet 
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  1. Allan, D. and Michell, R.H. (1974). Phosphatidylinositol Cleavage Catalysed by the Soluble Fraction from Lymphocytes. Biochem. J. 142, 591–597.Google Scholar
  2. Bell, R.L., Kennerly, D.A., Stanford, N. and Majerus, P.W. (1979). Diglyceride Lipase: A Pathway for Arachidonate Release from Human Platelets. Proc. Natl. Acad. Sci. USA 76, 3238–3241.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Billah, M.M., Lapetina, E.G. and Cuatrecasas, P. (1981). Phospholipase A2 Activity Specific for Phosphatidic Acid; A Possible Mechanism for the Production of Arachidonic Acid in Platelets. J. Biol. Chem. 256, 5399–5403.PubMedGoogle Scholar
  4. Bills, T.K., Smith, J.B. and Silver, J.M. (1977). Selective Release of Arachidonic Acid from Phospholipids of Human Platelets in Response to Thrombin. J. Clin. Invest. 60, 1–6.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Blackwell, G.J., Duncombe, W.G., Flower, R.J., Parsons, M.F. and Vane, J.R. (1977). The Distribution and Metabolism of Arachidonic Acid in Rabbit Platelets During Aggregation and Its Modification by Drugs. Br. J. Pharmacol. 59, 353–366.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Broekman, M.J., Ward, J.W. and Marcus, A.J. (1980). Phospholipid Metabolism in Stimulated Human Platelets, Change in Phosphatidylinositol, Phosphatidic Acid, and Lysophospholipids. J. Clin. Invest. 66, 275–283.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Chau, L-Y. and Tai, H-H. (1981). Release of Arachidonate from Diglyceride Requires the Sequential Action of Diglyceride Lipase and a Monoglyceride Lipase. Biochem. Biophys. Res. Commun. 100, 1688–1695.PubMedCrossRefGoogle Scholar
  8. Hanahan, D.J., Dempoulos, C.A., Liehr, J. and Pinckard, R.N. (1980). Identification of Platelet Activating Factor Isolated from Rabbit Basophils as Acetyl Glyceryl Ether Phosphorylcholine. J. Biol. Chem. 255, 5514–5516.PubMedGoogle Scholar
  9. Hirata, F., Corcoran, B.A., Venkatasubramanian, K., Schiffman, E. and Axelrod, J. (1979). Chemoattractants Stimulate Degradation of Methylated Phospholipids and Release of Arachidonic Acid in Rabbit Leukocytes. Proc. Natl. Acad. Sci. USA 76, 2640–2643.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Holub, B.J. and Kuksis, A. (1978). Metabolism of Molecular Species of Diacylglycerophospholipids. Adv. Lipid Res. 16, 1–15.Google Scholar
  11. Irvine, R.F. and Dawson, R.M.C. (1978). The Distribution of Calcium-dependent Phosphatidylinositol-specific Phosphodiesterase in Rat Brain. J. Neurochem. 31, 1427–1434.PubMedCrossRefGoogle Scholar
  12. Irvine, R.F. and Dawson, R.M.C. (1979). Neutral Phospholipase Hydrolysing Phosphatidylinositol and Their Possible Role in Stimulated Turnover of this Phospholipid. Biochem. Soc. Trans. 7, 353–357.PubMedCrossRefGoogle Scholar
  13. Jesse, R.L. and Franson, R.C. (1979). Modulation of Purified Phospholipase A2 Activity from Human Platelets by Calcium and Indomethacine. Biochim. Biophys. Acta 575, 467–470.CrossRefGoogle Scholar
  14. Kannagi, R. and Koizumi, K. (1978). Some Properties of Platelet Phospholipase A2; Its Mechanism of Activation. in Proceedings of XVIIth Congress of International Society of Hematology, Vol. 1, p. 266, Création Congrèss-Services, Brionne.Google Scholar
  15. Kannagi, R. and Koizumi, K. (1979a). Phospholipid-deacylating Enzymes of Rabbit Platelets. Arch. Biochem. Biophys. 196, 534–542.PubMedCrossRefGoogle Scholar
  16. Kannagi, R. and Koizumi, K. (1979b). Effect of Different Physical States of Phospholipid Substrates on Partially Purified Platelet Phospholipase A2 Activity. Biochim. Biophys. Acta 556, 423–433.PubMedCrossRefGoogle Scholar
  17. Kannagi, R. and Koizumi, K. (1979c). A Review on the Arachidonic Acid Metabolism and Phospholipases in Blood Platelets. (in Japanese) Jap. J. Clin. Pathol. 40, 101–116.Google Scholar
  18. Kannagi, R., Koizumi, K., Hata-Tanoue, S. and Masuda, T. (1980). Mobilization of Arachidonic Acid from Phosphatidylethanolamine Fraction to Phosphatidylcholine Fraction in Platelets. Biochem. Biophys. Res. Commun. 96, 711–718.PubMedCrossRefGoogle Scholar
  19. Kannagi, R., Koizumi, K. and Masuda, T. (1981). Limited Hydrolysis of Platelet Membrane Phospholipids, on the Proposed Phospholipase-susceptible Domain in Platelet Membranes. J. Biol. Chem. 256, 1177–1184.PubMedGoogle Scholar
  20. Mauco, G., Chap, H. and Douste-Blazy, L. (1979). Characterization and Properties of a Phosphatidylinositol Phosphodiesterase (Phospholipase C) from Platelet Cytosol. FEBS Lett. 100, 367–370.Google Scholar
  21. Nathan, I., Fleischer, G., Livne, A., Dvilansky, A. and Parola, H. (1979). Membrane Microenvironmental Changes During Activation of Human Blood Platelets by Thrombin, a Study With a Fluorescent Probe. J. Biol. Chem. 254, 9822–9828.PubMedGoogle Scholar
  22. Okuma, M., Yamashita, S. and Numa, S. (1973). Enzymic Studies on Phosphatidic Acid Synthesis in Human Platelets. Blood 41, 379–389.PubMedGoogle Scholar
  23. Op den Kamp, J.A.F., de Gier, J. and van Deenen, L.L.M. (1974). Hydrolysis of Phosphatidylcholine Liposomes by Pancreatic Phospholipase A2 at the Transition Temperature. Biochim. Biophys. Acta 345, 253–256.CrossRefGoogle Scholar
  24. Rittenhouse-Simmons, S. (1979). Production of Diglyceride from Phosphatidylinositol in Activated Human Platelets. J. Clin. Invest. 63, 580–587.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Rittenhouse-Simmons, S. (1981). Differential Activation of Platelet Phospholipases by Thrombin and Ionophore A 23187. J. Biol. Chem. 256, 4153–4155.PubMedGoogle Scholar
  26. Russell, F.A., and Deykin, D. (1976). The Effect of Thrombin inthe Uptake and Transformation of Arachidonic Acid by Human Platelets. Am. J. Hematol. 1, 59–70.PubMedCrossRefGoogle Scholar
  27. Samuelsson, B., Goldyine, M., Granstrom, E., Hamberg, M., Hammerström, S. and Malmsten, C. (1978). Prostaglandins and Thromboxanes. Annu. Rev. Biochem. 47, 997–1029.PubMedCrossRefGoogle Scholar
  28. Shattil, S.J., McDonough, M. and Burch, J.W. (1981). Inhibition of Platelet Phospholipid Methylation During Platelet Secretion. Blood 57, 537–544.PubMedGoogle Scholar
  29. Schick, P.K., Kurica, K.B. and Chako, G.K. (1976). Location of Phosphatidylethanolamine and Phosphatidylserine in the Human Platelet Plasma Membrane. J. Clin. Invest. 57, 1221–1226.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Schoene, N.W. and Iacono, J.M. (1973). Metabolism of Linoleic and Arachidonic Acid in Human Blood Platelets. Fed. Proc. 32, 919.Google Scholar
  31. Strong, P.N. and Kelly, R.B. (1977). Membranes Undergoing Phase Transition are Preferentially Hydrolyzed by beta-bungarotoxin. Biochim. Biophys. Acta 469, 231–235.CrossRefGoogle Scholar
  32. Takai, Y., Kishimoto, A., Kikkawa, U., Mori, T. and Nishizuka, Y. (1979). Unsaturated Diacylglycerol as a Possible Messenger for the Activation of Calcium-activated, Phospholipid-dependent Protein Kinase System. Biochem. Biophys. Res. Commun. 91, 1218–1224.PubMedCrossRefGoogle Scholar
  33. Van den Bosch, H. (1980). Intracellular Phospholipases A. Biochim. Biophys. Acta 604, 191–246.PubMedGoogle Scholar
  34. Van Zoelen, E.J.J., van Dijck, P.W.M., de Kruijff, B., Verkleij, A.J. and van Deenen, L.L.M. (1978). Effect of Glycophorin Incorporation on the Physico-chemical Properties of Phospholipid Bilayers. Biochim. Biophys. Acta 514, 9–24.PubMedCrossRefGoogle Scholar
  35. Verger, R. and de Haas, G.H. (1976). Interfacial Enzyme Kinetics of Lipolysis. Annu. Rev. Biophys. Bioeng. 5, 77–117.PubMedCrossRefGoogle Scholar
  36. Vogt, W. (1978). Role of Phospholipase A2 in Prostaglandin Formation. In Advances in Prostaglandin and Tromboxane Research, 3, (Eds., Galli, C., Galli, G., and Porcellati, G.), Raven Press, New York.Google Scholar
  37. Warren, G.B., Jouslay, M.D., Metcalfe, J.C. and Birdsall, N.J.M. (1975). Cholesterol is Excluded from the Phospholipid Annulus Surrounding an Active Calcium Transport Protein. Nature 255, 684–687.PubMedCrossRefGoogle Scholar
  38. Wykle, R.L., Malone, B. and Snyder, F. (1980). Enzymatic Synthesis of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, a Hypotensive and Platelet-aggregating Lipid. J. Biol. Chem. 255, 10256–10260.PubMedGoogle Scholar

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  • Reiji Kannagi

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