Platelet Agonists and Their Signaling Systems

Thrombin is the most potent physiologic platelet agonist, and induce all the platelet responses mentioned in section 9.3 and suppresses cAMP synthesis. Although thrombin is an enzyme, its ability to activate platelets depends on its concentration (Detwiler and Feinman, 1973). Harmon and Jamieson (1986) suggested that there are both high affinity 

Serotonin binds to the platelet 5-HTj receptor coupled to PLC via a G protein. The human serotonin receptor has been cloned and have the usual seven transmembrane domain form (Saltzman et al., 1991). Serotonin is rapidly taken up by passive diffusion and by a high affinity eneigy-dependent carrier, and is released upon platelet activation by secretion ftom the dense granules (Pletscher, 1987). 

Platdet-activating factor (PAF) is formed fi om the membrane phospholipid l-O-alkyl-2-acyl-sn-glycero-3-phosphocholine by the consecutive actions of PLAj and acyltransferase (Qiao and Olson, 1993) and binds to its receptor on human platelets oprogge and Akkerman, 1985 Kloprogge et al. 1986). Rat and mouse platelets lack this receptor (Bairea, 1984 Siess 1989). It has been shown that 87 % of the PAF produced is contained in the microvesicles that are shed fiom the platelets during the activation process (Iwamoto etal, 1996). 

Vasopressin bind to human platelets via V, vasopressin receptors and mediates activation of the polypho hoinositol metabolism via PLC, increase in [Ca ]j and aggregation (Pollock and MacMtyre, 1986 hiaba et al, 1988). 

Adrenaline is only capable of producing platelet aggregation in the presence of other platelet agonists (Steen cr of, 1993 Lanza et al, 1988), and is therefore not a tme agonist. Platelets have stimulatory Uj adrenoreceptors and inhibitory p adrenoreceptors, but the adrenoreceptors predcnnhiates. The adrenoreceptor is coupled via G proteins to adenylyl cyclase, while ffie a, adrenoreceptor (present in about 30 %) has Ireen proposed to be 

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