Diversity of Agonist-Mediated Signal Transduction Pathways in Human Platelets
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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).
KeywordsArachidonic Acid Platelet Aggregation Platelet Rich Plasma Human Platelet Myosin Light Chain Kinase
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