Agonists interaction with radiolabeled α-adrenoceptor antagonists binding sites in rat mesenteric artery

The nature of the postsynaptic α-adrenoceptors in vasculature has been a matter of debate with the differences in the observations from in vivo and in vitro experiments. These studies were done on the basis of the selectivity of the α-adrenoceptor agonists. In the present study, we investigated the nature of these agonists interaction with the [³H]prazosin and [³H]yohimbine binding sites in the plasma membrane vesicles of rat mesenteric artery. Phenylephrine and methozamine were used as the putative α₁-adrenoceptor agonists. Clonidine, naphazoline, B-HT 920, and UK-14.304 were used as the putative α₂-adrenoceptor agonists. All these agonists except B-HT 920 competed with similar affinity for the specific binding sites of [³H]prazosin and [³H]yohimbine. The order of the potency for the agonists in competing for [³H]prazosin binding sites was clonidine naphazoline UK-14.304 phenylephrine B-HT 920 methoxamine, and for the [³H]yohimbine binding sites, the order was clonidine naphazoline B-HT 920 UK-14.304 phenylephrine methoxamine, Similar pA2 values for prazosin and yohimbine were calculated regardless of whether α₁-selective agonist, methoxamine, or α₂-selective agonist. BT 920 were used. Putative α₂-adrenoceptor-selective agonists behave as partial agonists in Functional studies inhibiting just maximal responses to (α₁-adrenoceptor agonists and norepinephrine in a dose-dependent fashion. It is therefore concluded that in rat mesenteric artery, there are two distinct sites of interaction for the antagonists, prazosin and yohimbine, but the 4ap-adrenoceptor agonists interact nonselectively with a single site in such a way that they are capable of affecting binding of either antagonist. A model for the postsynaptic α-adrenoceptor as a macromolecule has been proposed.