Advertisement

Diversity of Agonist-Mediated Signal Transduction Pathways in Human Platelets

Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 407)

Abstract

Considerable advances have been made during the past decade in ascertaining the intracellular biochemical events that lead to activation and aggregation of platelets. Platelet aggregation plays an important role in hemostasis and thromboembolic disorders. This mainly takes place by the action of endogenous agonists like ADP, platelet activating factor (PAF), epinephrine, 5-hydroxytryptamine (5-HT) and arachidonic acid. Epinephrine and 5-HT interact with receptors coupled to Gi proteins on platelets and activation of these receptors suppresses the adenylyl cyclase activity (Brass et al., 1993; Newman, 1992). Receptors for PAF and ADP in human platelets are coupled with Gq-phospholipase C (Gq/PLC) pathway, activation of this leads to generation of second messengers, inositol-l,4,5-triphosphate (IP3) and diacylglyecrol (DAG) (Brass et al., 1993). IP3 causes release of calcium from internal stores and DAG activates protein kinase C (PKC). Inhibitory effects of PKC on receptor-mediated IP3 production and Ca++ mobilization are wide-spread and also occur in platelets (Heemskerk & Sage, 1994; Watson & Lapetina, 1985).

Keywords

Arachidonic Acid Platelet Aggregation Platelet Rich Plasma Human Platelet Myosin Light Chain Kinase 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Brass, L.F., Hoscie, J.A., and Manning, D.R., 1993, Thromb. Haemost. 70(1): 217–223.PubMedGoogle Scholar
  2. Bretschneider, E., Glusa, E., and Schror, K., 1994, Thrombo. Res., 5: 233–242.CrossRefGoogle Scholar
  3. Cross, M.J., Stewart, A., Hodgkin, M.N., Kerr, D.J. and Wakelam, M.J.O., 1995, J. Biol. Chem., 270(43): 25352–25355.PubMedCrossRefGoogle Scholar
  4. Hashimoto, Y., Ogihara, A., Nakanishi, S., Matsuda, Y., Kurokawa, K. and Nonomura, Y., 1992, J. Biol. Chem., 267(24): 17074–17081.Google Scholar
  5. Heemskerk, J.W.M., and Sage, S.O., 1994, Platelets, 5: 295–316.PubMedCrossRefGoogle Scholar
  6. Hourani, S.M.O., and Hall, D.A., 1994, Trends Pharmacol. Sci., 15: 103–108.PubMedCrossRefGoogle Scholar
  7. Newmann, M. E., 1992, Eur. J. Pharmacol., Mol. Pharmacol. Sec., 226: 281–285.CrossRefGoogle Scholar
  8. Rittenhouse, S. 1995, Seminar in Hematology, 32(2): 120–125.Google Scholar
  9. Shah, B.H., and Saeed, S.A., 1995, Res. Comm. Mol. Path. Pharmacol., 89(2): 157–164.Google Scholar
  10. Shah, B.H., McEwan, DJ., and Milligan, G., 1995, Proc. Natl. Acad. Sci. USA., 92: 1886–190.PubMedCrossRefGoogle Scholar
  11. Shah, B.H., and Milligan G., 1994, Mol. Pharmacol., 46: 1–7.PubMedGoogle Scholar
  12. Shah, B.H., Shamim, G., Khan, S. and Saeed, S., 1996, Biochem. Mol. Biol. Int., (in press).Google Scholar
  13. Thomason, P.A., James, S.R., Casey, P.J., and Downes, C.P., 1994, J. Biol. Chem., 269, 16525–16528.PubMedGoogle Scholar
  14. Turini, M.E., Gaudette, D.C., Holub, B.J., and Kirkland, J.B., 1993, Thromb. Haemostasis, 70: 648–653.Google Scholar
  15. Ui, M., Okada, T., Hazeki, K., and Hazeki, O., 1995, Trends Biochem. Sci., 20: 303–307.PubMedCrossRefGoogle Scholar
  16. Watson S.P., and Lapetina, E.G., 1985, Proc. Natl. Acd. Sci., (USA), 82:2623–2626.CrossRefGoogle Scholar
  17. Yatomi, Y., Hazeki, O., Kume, S. and Ui, M., 1992 Biochem. J., 285: 745–751.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  1. 1.Department of Physiology and PharmacologyThe Aga Khan UniversityKarachiPakistan

Personalised recommendations