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Binding studies with [125I]epinephrine to the human platelet alpha2-adrenergic receptor have been performed. Epinephrine bound to the platelet adrenoceptors, indicating the presence of an alpha2-adrenoceptor subtype on human platelets. The association of [125I]epinephrine to the platelet adrenoceptor was rapid and saturable. Increasing concentrations of GTP shifted the binding of epinephrine to a higher affinity state (KD = 38.4 +/- 3.1 pM and Bmax = 17.5 +/- 1.0 fmol/10(7) platelets). The addition of 10 microM guanosine 5′-O-thiodiphosphate (GDPbetaS) to the platelet-rich plasma resulted in a loss of epinephrine binding. The potency profile of dopamine-related compounds to inhibit the binding of [125I]epinephrine to the platelet adrenoceptors at 3 microM binding revealed some stereoselectivity for dopamine D2 agonists. The dopamine D2 receptor antagonists, (-)-sulpiride and clozapine, inhibited the binding of [125I]epinephrine at 100 microM. A similar profile was obtained at 10 microM, with the highest inhibition being observed for (-)-sulpiride. The results of the present study indicate that: (1) epinephrine binds to the platelet alpha2-adrenoceptor, (2) the presence of GTP favors the binding of epinephrine to the platelet adrenoceptors, (3) dopamine D2 agonists inhibited the binding of [125I
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