This study evaluated the mechanism of epinephrine potentiation of platelet secretion induced by thromboxane A2 (TXA2). Dog platelets that do not secrete in response to TXA2 alone (TXA2-) were compared with dog platelets that do secrete (TXA2+) and with human platelets. TXA2- platelets had impaired TXA2 receptor (TP receptor)-G protein coupling, indicated by 1) impaired stimulated GTPase activity, 2) elevated basal guanosine 5'-O-(3-thiotriphosphate) binding, and 3) elevated Gα(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. TXA2- and TP receptor-desensitized TXA2+ dog and human platelets had altered ligand binding parameters compared with untreated TXA2+ or human platelets. These parameters were reversed, along with impaired secretion, by epinephrine. Basal phosphorylation of TXA2- platelet TP receptors was elevated 60% and was normalized by epinephrine. Epinephrine potentiates platelet secretion stimulated by TXA2 by reducing basal TP receptor phosphorylation and facilitating TP receptor-G protein coupling in TXA2- platelets and, probably, in normal platelets as well.
- G proteins
- Platelet activation