Specific Binding of Tritium-Labeled Platelet-Activating Factor to Human Mononuclear Leukocyte Membranes: A Third Putative Receptor of Platelet-Activating Factor

  • San-Bao Hwang
  • My-Hanh Lam
  • Kenneth Wu
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Platelet-activating factor (PAF) is a potent phospholipid mediator with a wide spectrum of biological activities (Braquet et al., 1987; Snyder, 1989). It was initially identified as a platelet aggregating soluble product released by immunoglobulin E-sensitized rabbit basophils (Benveniste et al., 1972) and was subsequently identified as 1-0-alkyl- 2-acetyl-sn-glyceryl-3-phosphorylcholine (Demopoulos et al., 1979; Benveniste et al., 1979; Blank et al., 1979). The structural requirements for PAF biological actions are highly specific. Very low, concentrations of PAF are usually required to trigger biological effects. Also, specific desensitization takes place after exposure of cells or tissues to PAF. Specific receptors responsible for transducing a stimulatory signals within the cells are therefore suspected.


Platelet Activate Factor Human Monocyte Human Platelet Mononuclear Leukocyte Rabbit Platelet 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Benveniste, J.Henson, P. M., and Cochane, C. G., 1972, Leukocyte-dependent histamine release from rabbit platelets: the role of IgE, basophils, and a platelet-activating factor, J. Exp. Med., 136: 1356.Google Scholar
  2. Benveniste, J.,Tence, M., Bidault, J., Boullet, C., and Polonsky, J., 1979, Semisynthese et structure proposee du facteur activant les plaquettes (PAF). PAF acether, un alkyl ether analog de la lysophosphatidylcholine, C.R. Acad. Sci. Paris, D289: 1037.Google Scholar
  3. Blank, M.L., Snyder, F., Byer, L.W., Brooks, B., and Muirhead, E.E., 1979, Antihypertensive activity of an alkyl ether analog of phosphatidylcholine, Biochem. Biophvs. Res. Commun., 90: 1194.Google Scholar
  4. Braquet, P.Touqui, L., Shen, T.Y., and Vargaftig, B.B., 1987, Perspectives in platelet-activating factor research, Pharmacol. Rev., 39: 97.Google Scholar
  5. Boyum, A. 1968, Isolation of mononuclear cells and granulocytes from human blood: isolation of mononuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedmentation at 1 g, Scand. J. Clin. Lab. Invest., 21 (Suppl. 97): 77.Google Scholar
  6. Cheng, Y.and Prusoff, W.H., 1973, Relationship between the inhibition constant (Ki) and the concentration of inhibitor which cause 50% inhibition (I50) of an enzyme reaction, Biochem. Pharmacol., 22: 3099.Google Scholar
  7. Demopoulos, A., Pinckard, R.N., and Hanahan, D.J., 1979, Platelet-activating factor. Evidence for 1-O-alkyl-2-acetyl-sn-glyceryl-3phosphocholine as the active component (a new class of lipid chemical mediators), J. Biol. Chem., 254: 9355.Google Scholar
  8. Honda, Z.-I., Nakamura, M., Miki, I., Minami, M., Watanabe, T., Seyama, Y., Okado, H., Toh, H., Ito, K., Miyamoto, T., and Shimizu, T., 1991, Cloning by functional expression of platelet-activating factor receptor from guinea-pig lung, Nature, 349: 342.PubMedCrossRefGoogle Scholar
  9. Hwang, S.-B., 1988, Identification of a second putative receptor of platelet-activating factor from human polymorphonuclear leukocytes, J. Biol. Chem., 263: 3225.Google Scholar
  10. Hwang, S.-B., 1990, Specific receptors of platelet-activating factor, receptor heterogeneity, and signal transduction mechanisms, J. Lipid Mediators, 2: 123.Google Scholar
  11. Hwang, S.-B., 1991, High affinity receptor binding of platelet-activating factor in rat peritoneal polymorphonuclear leukocytes, Europ. J. Pharmacol., in press.Google Scholar
  12. Hwang, S.-B., and Lam, M.-H., 1986, Species difference in the specific receptor of platelet activating factor, Biochem. Pharmacol., 35: 4511.Google Scholar
  13. Hwang, S.-B., Lam, M.-H., Biftu, T., Beattie, T.R., and Shen, T.Y., 1985, 2,5-bis(3,4,5-trimethoxyphenyl) tetrahydrofuran. An orally active specific and competitive receptor antagonist of platelet activating factor, J. Biol. Chem., 260: 15639.Google Scholar
  14. Hwang, S.-B., Lam, M.-H., and Chang, M.N., 1986a, Specific binding of [3H]dihydrokadsurenone to rabbit platelet membranes and its inhibition by the receptor agonists and antagonists of platelet-activating factor, J. Biol. Chem., 261: 13720.Google Scholar
  15. Hwang, S.-B., Lam, M.-H., and Pong, S.S., 1986b, Ionic and GTP regulation of binding of platelet-activating factor to receptors and platelet-activating factor-induced activation of GTPase in rabbit platelet membranes, J. Biol. Chem., 261: 532.Google Scholar
  16. Hwang, S.-B., Lee, C.S.C., Cheah, M.J., and Shen, T.Y., 1983, Specific receptor sites for 1–0-alkyl-2–0-acetyl-sn-glycero-3phosphocholine (platelet activating factor) on rabbit platelet and guinea pig smooth muscle membranes, Biochemistry, 22: 47–56.CrossRefGoogle Scholar
  17. Hwang, S.-B., and Wang, S., 1990, Receptor heterogeneity and the existence of intracellular receptors of platelet-activating factor. in: “Platelet-activating Factor Antagonists: New Developments and Clinical Application,” J.T. O’Flaherty & P. Ramwell, eds., Portfolio Publishing Co., The Woodlands, TX.Google Scholar
  18. Jacobs, S., Chang, K.-J., and Cuatrecasas, P., 1975, Estimation of hormone receptor affinity by competitive displacement of labeled ligand: effect of concentration of receptor and the labeled ligand, Biochem. Biophys. Res. Commun., 66: 687.Google Scholar
  19. Kroegel, C., Yakawa, T., Westwick, J., and Barnes, P.J., 1989, Evidence for two platelet activating factor receptors on eosinophils: Dissociation between PAF-induced intracellular calcium mobilization and degranulation and superoxides anion generation in eosinophils, Biochem. Biophys. Res. Commun., 162: 511.Google Scholar
  20. Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R.J.,1951, Protein measurement with the Folin phenol reagent, J. Biol. Chem., 193: 265.Google Scholar
  21. Marcheselli, V.L., Rossowska, M.J., Domingo, M.-T., Braquet P., and Bazan, N.G., 1990, Distinct platelet-activating factor binding sites in synaptic endings and in intracellular membranes of rat cerebral cortex, J. Biol. Chem., 265: 9140.Google Scholar
  22. Naccache, P.H., Molski, M.M., Volpi, M., Becker, E.L., and Sha’afi, R.I., 1985, Unique inhibitory profile of platelet activating factor induced calcium mobilization, polyphosphoinositide turnover and granule enzyme secretion in rabbit neutrophile towards pertussis toxin and phorbol ester, Biochem. Biophvs. Res. Commun., 130: 677.Google Scholar
  23. Ng, D.S., and Wong, K., 1988, Specific binding of platelet-activating factor (PAF) by human peripheral blood mononuclear leukocytes, Biochem. Biophvs. Res. Commun., 155: 311.Google Scholar
  24. Ng, D.S., and Wong, K., 1989, Effect of platelet-activating factor (PAF) on cytosolic free calcium in human peripheral blood mononuclear leukocytes, Res. Commun. Chem. Pathol. Pharmacol., 64: 351.Google Scholar
  25. Nunez, D., Kumar, R., and Hanahan, D.J., 1989, Inhibition of [3H]platelet activating factor (PAF) by Zn2+: a possible explanation for its specific PAF antiaggregating effects in human platelets, Arch. Biochem. Biophvs., 272: 466.Google Scholar
  26. Ponpipom, M.M., Hwang, S.-B., Doebber, T.W., Acton, J.J., Alberts, A.W., Biftu, T., Brooker, D.R., Bugianesi, R.L., Chabala, J.D., Gamble, N.L., Graham, D.W., Lam, M.-H., and Wu, M.S., 1988, ()-Trans-2(3methoxy-5-methylsulfonyl-4-propoxyphenyl)-5-(3,4,5trimethoxyphenyl) tetrahydrofuran (L-659,989), a novel, potent PAF receptor antagonist, Biochem. Biophys. Res. Commun., 150: 1213.Google Scholar
  27. Snyder, F., 1989, Biochemistry of platelet-activating factor: A unique class of biologically active phospholipids, Proc. Soc. Exp. Biol. Med., 190: 125.Google Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • San-Bao Hwang
    • 1
  • My-Hanh Lam
    • 1
  • Kenneth Wu
    • 1
  1. 1.Merck Sharp & Dohme Research LaboratoriesAtherosclerosis Research DepartmentRahwayUSA

Personalised recommendations