correction of impaired platelet thromboxane receptor signaling. Am J Physiol Cell Physiol 279: C1760-C1771, 2000.-This study evaluated the mechanism of epinephrine potentiation of platelet secretion induced by thromboxane A 2 (TXA 2 ). Dog platelets that do not secrete in response to TXA 2 alone (TXA 2 Ϫ) were compared with dog platelets that do secrete (TXA 2 ϩ) and with human platelets. TXA 2 Ϫ platelets had impaired TXA 2 receptor (TP receptor)-G protein coupling, indicated by 1) impaired

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... mulated GTPase activity, 2) elevated basal guanosine 5Ј-O-(3thiotriphosphate) binding, and 3) elevated G␣ q palmitate turnover that was corrected by preexposure to epinephrine. Kinetic agonist binding studies revealed biphasic dog and human platelet TP receptor association and dissociation. TXA 2 Ϫ and TP receptor-desensitized TXA 2 ϩ dog and human platelets had altered ligand binding parameters compared with untreated TXA 2 ϩ or human platelets. These parameters were reversed, along with impaired secretion, by epinephrine. Basal phosphorylation of TXA 2 Ϫ platelet TP receptors was elevated 60% and was normalized by epinephrine. Epinephrine potentiates platelet secretion stimulated by TXA 2 by reducing basal TP receptor phosphorylation and facilitating TP receptor-G protein coupling in TXA 2 Ϫ platelets and, probably, in normal platelets as well. G proteins; dogs; platelet activation EPINEPHRINE BINDS to ␣ 2 -adrenergic receptors (␣ 2 -AR) and stimulates variable human platelet aggregation and secretion, and it potentiates other agonist-induced platelet activation in human and dog platelets (2, 21, 22, 26, 41) . The mechanism of epinephrine-induced platelet activation has been the subject of numerous studies and considerable debate (see Ref. 41 for review). Previous investigations indicated that epinephrine did not function as a single platelet agonist but, rather, that it enhanced the activation initiated by other agonists (2, 26, 41) . Banga et al. (2) found that epinephrine promoted human platelet aggregation and secretion by increasing thromboxane A 2 (TXA 2 ) formation, via activation of phospholipase A 2 , and by facilitating TXA 2 -mediated signaling. The mechanism responsible for the latter effect was not defined, but it was suggested that epinephrine potentiated platelet