Platelet agonist, epinephrine

Many platelet agonists, such as ADF) TXA2, epinephrine, serotonin, and thrombin, interact with specific transmembrane receptors that are coupled to G-proteins, initiating several signaling pathways that lead to PLC activation ending in platelets shape change and granule secretion (Fig. 4). 

Defects in platelet-agonist interaction are exemplified by patients with impaired responses because of an abnormality at the level of platelet surface receptors for a specific agonist. Such receptor defects have been documented for epinephrine, collagert, ADP, and thromboxane A2. Hirata et al (21) have described an Arg 60 to Leu mutation of the human thromboxane A2 receptor in a dominantly inherited bleeding disorder. Evidence has been... 

Although this model was consistent with results obtained using A23187, which is known to alter intracellular cation gradients (18,19J, a similar mechanism of action by physiological platelet agonists, e.g. ADP, epinephrine, thrombin,... 

Epinephrine-stimulated Ca2 influx. Our results with D2O also provided evidence that a different platelet agonist i.e. epinephrine, does not act through the same mechanism of Ca2 mobilization as does ADP. In this regard, D2O was not found to be effective in blocking epinephrine-induced platelet activation (29). Therefore, we investigated the possibility that epinephrine, in contrast to ADP, increases platelet membrane permeability to Ca2. Using trace amounts of 45Ca it was demonstrated that epinephrine does in fact induce a transmembrane Ca2 influx which is concomitant with the... 

Platelets can be activated by a variety of agents including the physiologic agonists ADP, thromboxane A2, epinephrine, collagen, and thrombin. Platelet activation is generally associated with a change in platelet shape (except for epinephrine-induced platelet activation) from discs to spiny spheres with pseudopodia. Platelet pseudopod formation is dependent on actin polymerization in the activated platelets. The interaction of actin filaments with myosin, mediated by calcium (9), facilitates platelet contractile activity (e.g., clot retraction). 

Epinephrine activates platelets through the a-adrenergic receptor coupled to a G-protein receptor, It is proposed that this agonist shares with ADP the P2Y 2 receptor signaling (16). 

Studies by Scmtton et. al. and Stormoiken and his associates, have shown compromised functional response to epinephrine in apparently normal individuals (52,53). Weiss et. al. have described secretion defects from patients with bleeding disorders (54). White et. al. have followed functional response of platelets of patients with diabetes and Hermasky-Pudlak Syndrome (HPS) whose platelets lack dense bodies. Platelets of patients with HPS exhibit compromised response to the action of agonists (55). Hardisty et. al., and Ware and associates, have provided further evidence for altered signal transduction mechanisms. These and other studies seem to suggest that an impaired intracellular calcium flux may be the chief cause of platelet dysfunction (56-58, discussed in other chapters). 

Shattil SJ, Bud shi A, Scrutton MC. Epinephrine induces platelet fibrinogen receptor expression, fibrinogen binding, and aggregation in whole blood in the Asence of other excitatory agonists. Blood 1989 73 150-158. 

In general, ruminant platelets are less responsive to agonists compared to platelets of other species (Bondy and Gentry 1989). Bovine platelets are more sensitive to stimulation by PAF than by ADP or thrombin. ADP-induced aggregation does not induce dense granule secretion. Epinephrine, arachadonic acid, and serotonin do not aggregate bovine platelets... 

Serotonin is a strong agonist for cat platelets and induces a biphasic aggregation response (Tschopp 1970). Response to serotonin is coupled to formation of thromboxane Bjand dense granule secretion. The serotonin receptor on cat platelets binds more serotonin than do platelets other species (Leysen et al. 1983). Epinephrine potentiates aggregation responses to other agonists. 

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