Skip to main content
SpringerLink
Log in

Platelet-Activating Factor and Calcium Signaling: Its Implication in Cellular Responses

  • Chapter
Cell Signal Transduction, Second Messengers, and Protein Phosphorylation in Health and Disease

  • 64 Accesses

Summary

Platelet-activating factor (PAF), a potent phospholipid inflammatory mediator, known to affect cellular phosphoinositide metabolism, through formation of inositol triphosphate, transiently releases intracellular calcium. This highly sensitive cellular signaling process is involved in a great variety of cellular responses in many organs, and it may play a pivotal role in regulating meditor release in the cell. Through activating phospholipase A2, leading to arachidonic acid release and eicosanoid generation, PAF may induce downregulation of mediator release, an important process to maintain normal cell metabolism. On the other hand, via interacting with various cytokines or bacterial lipopolysaccharides, PAF may up-regulate mediator release, initiating an important role for the phospholipid noy only under normal conditions, but also in pathophysiological alterations of cellular responses and metabolism.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 16.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  • Abigail, F., Brotherton, A., and Hoack, J.C. (1982). Role of Ca2+ and cyclic AMP in the regulation of the production of prostacyclin by the vascular endothelium. Proc. Natl. Acad. Sci. USA 79: 495–499.

    Article  Google Scholar 

  • Aepfelbacher, M., Ziegler-Heitbrock, H.W., Lux, I., and Weber, P.C. (1992). Bacterial lipopolysaccharide up-regulates platelet-activating factor stimulated Ca2+ mobilization and eicosanoid release in human Mono Mac 6 cells. J. Immunol. 148: 2186–2193.

    PubMed  CAS  Google Scholar 

  • Berridge, M.J. (1993a). Inositol triphosphate and calcium signalling. Nature 361: 315–325.

    Article  PubMed  CAS  Google Scholar 

  • Berridge, M.J. (1993b). A tale of two messengers. Nature 365: 388–389.

    Article  PubMed  CAS  Google Scholar 

  • Billah M.M. anf Lapetina, E.G. (1983). Platelet-activating factor stimulates metabolism of phosphoinositides in horse platelets: Possible relationship to Ca2+ mobilization during stimulation. Proc. Natl. Acad. Sci. USA 80: 965–968.

    Article  PubMed  CAS  Google Scholar 

  • Billah, M.M. and Siegel, M.I. (1984). Calmodulin antagonists inhibit formation of plateletactivating factor in stimulated human neutrophils. Biochem. Biophys. Res. Commun. 118: 629–635.

    Article  PubMed  CAS  Google Scholar 

  • Bito, H., Nakamura, M., Honda, Z., Izumi, T., Iwatsubo, T., Seyama, Y., Ogura, A., Kudo, V., and Shimizu, T. (1992). Platelet-activating factor (PAF) receptor in rat brain: PAF metabolizes intracellular Ca2+ in hippocampal neurons. Neuron 9: 285–294.

    Article  PubMed  CAS  Google Scholar 

  • Braquet, P., Hosford, D., Koltz, P., Gilbaud, J., and Paubert-Braquet, M. (1990). Effect of platelet-activating factor on tumor necrosis factor-induced superoxide generation from human neutrophils. Possible involvement of G proteins. Lipids 26: 1071–1074.

    Article  Google Scholar 

  • Braquet, P., Paubert-Braquet, M., Bourgain, R., Bussolino, F., and Hosford, D. (1989a) PAF/cytokine autogenerated feedback networks in microvascular immune injury: consequences in shock, ischemia and graft rejection. J. Lipid Med. 1: 75–112.

    CAS  Google Scholar 

  • Braquet, P., Paubert-Braquet, M., Koltai, M., Bourgain, R., Bussolino, F., and Hosford. D. (1989b). Is there a case for PAF antagonists in the treatment of ischemic states? Trends Pharmacol. Sci. 10: 23–30.

    Article  PubMed  CAS  Google Scholar 

  • Braquet, P., Touqui, L., Shen, T.S., and Vargaftig, B.B. (1987). Perspectives in plateletactivating factor research. Pharmacol. Rev. 39: 97–145.

    PubMed  CAS  Google Scholar 

  • Catalan, R.E., Martinez, A.M., Aragones, M.D., Fernandez, I., Lombardia, M., and Miguel, E.G. (1992). PAF-induced activation of polyphosphoinositide-hydrolyzing phospholipase C in cerebral cortex. Biochem. Biophys. Res. Commun. 183: 300–305.

    Article  PubMed  CAS  Google Scholar 

  • Chiba, Y., Mikoda, N., Kawasaki, H., and Ito, K. (1990). Endothelium-dependent relaxant action of platelet activating factor in the rat mesenteric artery. Naunyn-Schmiedeberg’s Archs Pharmacol. 341: 68–73.

    CAS  Google Scholar 

  • Clark, G.D., Happel, L.T., Zorumski, C.F., and Bazan, N.G. (1992). Enhancement of hippocampal excitatory synaptic transmission by platelet-activating factor. Neuron 9: 1211–1216.

    Article  PubMed  CAS  Google Scholar 

  • Clement, M.G., Albertini, M., Dimori, M., and Aguggini, G. (1992). PAF and the role of vagus nerve in the breathing pattern of the pig. Prostagl. Leuk. Essent. Fatty Acids 45: 143–149,

    Article  CAS  Google Scholar 

  • Collins, S. (1993). Molecular structure of G-protein-coupled receptors and regulation of their expression. DN&P 6: 480–487.

    Google Scholar 

  • Conrad, G.W. and Rink, T.J. (1986). Platelet-activating factor raises intracellular calcium ion concentration in macrophages. J. Cell Biol. 103: 439–450.

    Article  PubMed  CAS  Google Scholar 

  • Edwards, G. and Weston, A.H. (1993). The pharmacology of ATP-sensitive K-channels. Annu. Rev. Pharmacol. Toxicol. 33: 597–637.

    CAS  Google Scholar 

  • Forstermann, U., Pollock, J.S., Schmidt, H.H.H.W., Heller, M., and Murad, F. (1991). Calmodulin-dependent endothelium-derived relaxing factor/nitric oxide synthase activity is present in the particulate and cytosolic fractions of bovine aortic endothelial cells. Proc. Natl. Acad. Sci. USA 88: 1788–1792.

    Article  PubMed  CAS  Google Scholar 

  • Gorman, R.R., Bunting, S., and Miller, O.V. (1977). Modulation of human platelet adenylate cyclase by prostacyclin (PGX). Prostaglandins 13: 377–388.

    Article  PubMed  CAS  Google Scholar 

  • Hall, LP. (1993). Inositol phosphates, cyclic AMP and signal transduction. DN&P 6: 5– 11.

    Google Scholar 

  • Hanahan, D.J., Demopoulos, C.A., Liehr, J., and Pinckard, R.N. (1980). Identification of platelet-activating factor isolated from rabbit J. Biol. Chem. 255: 5514–5516.

    PubMed  CAS  Google Scholar 

  • Harnett, M.M. and Klaus, G.G.B. (1988). G protein coupling of antigen receptorstimulated phosphatidylinositol hydrolysis in B cells. J. Immunol. 140: 3135–3139.

    PubMed  CAS  Google Scholar 

  • Homma, H. and Hanahan, D.J. (1988). Attenuation of platelet-activating factor (PAF)-induced stimulation of rabbit GTPase by phorbol ester, dibutyryl cAMP,and desensitization: concomitant effects on PAF receptor binding charecteristics. Arch. Biochem. Biophys. 262: 32–39.

    Article  PubMed  CAS  Google Scholar 

  • Hwang, S.-B. and Lim, M.-H. (1986). Ionic and GTP regulation of binding of plateletactivating factor to receptors and platelet-activating factor-induced activation of GTPase in rabbit platelet membranes. J. Biol. Chem. 261: 532–537.

    PubMed  CAS  Google Scholar 

  • Kamata, K., Mori, T., Shigenobu, K., and Kasuya, Y. (1989). Endothelium-dependent vasodilator effects of platelet activating factor on rat resistance vessels. Br. J.Pharmacol. 98: 1360–1364.

    Article  PubMed  CAS  Google Scholar 

  • Kecskemeti V. and Braquet, P. (1992). Cellular electrophysiological effects of plateletactivating factor (PAF) and its antagonist BN 52921 in cardiac preparations. Drugs Exptl. Clin. Res. 18: 23–27.

    Google Scholar 

  • Koltai, M., Hosford, D., Guinot, P., Esanu. A., and Braquet, P. (1991a). Plateletactivating factor (PAF): a review of its effects. antagonists and possible future clinical applications. Drugs 42 (Part I): 9–29.

    Article  PubMed  CAS  Google Scholar 

  • Koltai, M., Hosford, D., Guinot, P., Esanu, A., and Braquet, P. (1991b). Plateletactivating factor (PAF): a review of its effects, antagonists and possible future clinical applications. Drugs 42 (Part II): 174–204.

    Article  PubMed  CAS  Google Scholar 

  • Koltai, M., Tosaki, A., Guillon, J.-M., Hosford, D., and Braquet, P. (1989). PAF antagonists as potential therapeutic agents in cardiac anaphylaxis and myocardial ischemia. Cardiovasc. Drugs Rev. 7: 177–198.

    Article  Google Scholar 

  • Kuijpers, T.W., Hakkert, B.C., Hoogerwerf, M., Leeuwenberg J.F.M., and Roos,D.(1991). Role of endothelial leukocyte adhesion molecule-1 and platelet-activating factor in neutrophil adherence to IL-1-prestimulated endothelial cells: Endothelial Leukocyte adhesion molecule-1-mediated CD18 activation. J. Immunol. 147: 1369–1376.

    PubMed  CAS  Google Scholar 

  • Kunievsky, B. and Yavin, E. (1992). Platelet-activating factor stimulates arachidonic acid release and enhances thromboxane B2 production in intact fetal rat brain ex vivo. J.Pharmacol. Exp. Ther. 263: 562–568.

    PubMed  CAS  Google Scholar 

  • Lee, N.H. & Kerlavage, A.R. (1993). Molecular biology of G-protein-coupled receptors.D.N.&P. 6: 488–497.

    Google Scholar 

  • Mazer, B.D., Domenico, J., Sawami, H., and Gelfand, E.W. (1991). Platelet-activating factor induces an increase in intracellular calcium and expression of regulatory genes in human lymphoblastoid cells. J. Immunol. 146: 1914–1920.

    PubMed  CAS  Google Scholar 

  • Mazer, B.D., Sawami, H., Tordai, A., Gelfand, E.W. (1992). Platelet-activating factormediatedtransmembrane signaling in human B lymphocytes is regulated through a Pertussis-and Cholera toxin-sensitive pathway. J. Clin. Invest. 90: 759–765.

    Article  PubMed  CAS  Google Scholar 

  • Miller, L.G., Bazan, N.G., Roy, R.B., Clostre, F., Gaver, A., and Braquet, P. (1991).Platelet activating factor antagonists interact with GABAA receptors. Res.Commun. Chem. Pathol. Pharmacol. 74: 253–256.

    PubMed  CAS  Google Scholar 

  • Maudsley, D.J. and Morris, A.G. (1987). Rapid intracellular calcium changes in U937 monocyte cell line: transient inncrease in response to platelet-activatng faactor aand chemotactic peptide but not interferon or lipopolysaccharide. Immunology 61: 189–194.

    PubMed  CAS  Google Scholar 

  • Moritoki, H., Hisayama, T., Takeuchi, S., Miyano, H., and Kondoh, W. (1992).Involvement of nitric oxide pathway in the PAF-induced relaxation of rat thoracic aorta. Br. J. Pharmacol. 107: 196–201.

    Article  PubMed  CAS  Google Scholar 

  • Nakamura, M., Honda, Z., Waga, T., Matsumoto, T., Noma, M., and Shimizu, T.(1992). Endotoxin transduces Ca2+ signalling via platelet-activating factor receptor.FEBS-Lett. 314: 125–129.

    Article  PubMed  CAS  Google Scholar 

  • Nussler, A.K., Di Silvio, M., Billiar, T.R., Hoffman, R.A., Geller, D.A., Selby, R.,Madariaga, J., and Simmons, R.L. (1992). Stimulation of nitric oxide synthase pathway in human hepatocytes by cytokines and endotoxin. J. Exp. Med. 176:261–264.

    Article  PubMed  CAS  Google Scholar 

  • Paubert-Braquet, M., Hosford, D., Koltz, P., Guilbaud, J., and Braquet, P. (1991).Tumor necrosis factor primes PAF-induced superoxide production by human neutrophils: possible involvement of G proteins. J. Lipid Mediators 2: S1–S14.

    Google Scholar 

  • Pedemonte, C.H. (1993). Structure-function relationship of membrane ion pumps.D.N.&P. 6: 498–507.

    Google Scholar 

  • Prescott, S.M. Zimmerman, G.A., and McIntyre, T.M. (1990). Platelet-activating factor.J. Biol. Chem. 265: 1781–1784.

    Google Scholar 

  • Rees, D.D., Palmer, R.M.J., Schulz, R., Hodson, H.F., and Moncada, S. (1990).Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br. J. Pharmacol. 101: 746–752.

    Article  PubMed  CAS  Google Scholar 

  • Rink, T.J. and Sage, S.O. (1990). Calcium signaling in human platelets. Annu. Rev.Physiol. 52: 431–446.

    Article  PubMed  CAS  Google Scholar 

  • Schleiffenbaum, B. and Fehr, J. (1990). The tumor necrosis factor receptor and human neutrophil function. Deactivation and cross-deactivation of tumor necrosis factorinduced neutrophil responses by receptor down-regulation. J. Clin. Invest.86:184–95.

    Article  PubMed  CAS  Google Scholar 

  • Schulam, P.G., Putcha, G., Franklin-Johnson, J., and Schearer, W.T. (1990). Evidence for a platelet-activating factor receptor on human lymphoblastoid B cells activation of phosphoinositol cycle and induction of calcium mobilization. Biochem. Biophys.Res. Commun. 166: 1047–1052.

    Article  PubMed  CAS  Google Scholar 

  • Shukla, S.D. and Hanahan, D.J. (1983). An early decrease in phosphatidylinositol 4,5biphosphate upon stimulation of rabbit platelets with acetylglycerylether phosphorylcholine (platelet activating factor). Arch. Biochem. Biophys. 227: 626–629.

    Article  PubMed  CAS  Google Scholar 

  • Tateson, J.E., Moncada, S., and Vane, J.R. (1977). Effects of prostacyclin (PGX) on cyclic AMP concentrations in human platelets. Prostaglandins 13: 389–397.

    Article  PubMed  CAS  Google Scholar 

  • Tseng, G.-N. and Hoffmann, B.F. (1989). Two components of transient outward current in canine ventricular myocytes. Circ. Res. 64: 633–647.

    Article  PubMed  CAS  Google Scholar 

  • Van Willingen, G. and Akkerman, J.-W.N. (1991) Protein kinase C and cyclic AMP regulate reversible exposure of binding sites for fibrinogen on the glycoprotein IIB-IIIA complex of human platelets. Biochem. J. 273: 115–120.

    Google Scholar 

  • Ward, S.G. and Westnick, J. (1988). Antagonism of the platelet activating factor-induced rise of the intracellular calcium ion concentration of U337 cells. Br. J. Pharmacol.93: 769–774.

    Article  PubMed  CAS  Google Scholar 

  • Willard, A.L. (1992). Excitatory and neurotoxic actions of platelet-activating factor on rat myenteric neurons in cell culture. Ann. N. Y. Acad. Sci. 664: 284–292.

    Article  PubMed  CAS  Google Scholar 

  • Yue, T.L., Gleason, M.M., Hallenbeck, J., and Feuerstein, G. (1991a). Characterization of platelet-activating factor-induced elevation of cytosolic free calcium level in neurohybrid NCB-20 cells. Neuroscience 41: 177–185.

    Article  PubMed  CAS  Google Scholar 

  • Yue, T.L., Gu, J.L., and Feuerstein, G. (1992a). Protein kinase C activator phorbol 12, 13-dibutyrate inhibits platelet activating factor-stimulated Ca2+ mobilization and phosphoinositide turnover in neurohybrid NG108-15 cells. Neurochem. Res. 17: 997–1004.

    Article  PubMed  CAS  Google Scholar 

  • Yue, T.L., Stadel, J.M., Sarau, H.M., Friedman, E., Gu, J.L., Powers, D.A., Gleason, M.M., Feuerstein, G., and Wang, H.Y. (1992b). Platelet-activating factor stimulates phosphoinositide turnover in neurohybrid NCB-20 cells: involvement of pertussis toxin-sensitive guanine nucleotide-binding proteins and inhibition of protein kinase C. Mol. Pharmacol. 41: 281–289.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut Henri Beaufour, Le Plessis Robinson, France

    Matyas Koltai, David Hosford & Pierre G. Braquet

Authors
  1. Matyas Koltai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Hosford
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pierre G. Braquet
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Royal Academy of Sciences of Spain, Madrid, Spain

    A. Martin Municio

  2. Complutense University of Madrid, Madrid, Spain

    M. Teresa Miras-Portugal

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer Science+Business Media New York

About this chapter

Cite this chapter

Koltai, M., Hosford, D., Braquet, P.G. (1994). Platelet-Activating Factor and Calcium Signaling: Its Implication in Cellular Responses. In: Municio, A.M., Miras-Portugal, M.T. (eds) Cell Signal Transduction, Second Messengers, and Protein Phosphorylation in Health and Disease. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1879-2_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-1879-2_10

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5765-0

  • Online ISBN: 978-1-4615-1879-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation