Agonists interaction with radiolabeled alpha-adrenoceptor antagonists binding sites in rat mesenteric artery.
The nature of the postsynaptic alpha-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 alpha-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 methoxamine were used as the putative alpha 1-adrenoceptor agonists. Clonidine, naphazoline, B-HT 920, and UK-14,304 were used as the putative alpha 2-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 greater than naphazoline greater than UK-14,304 greater than phenylephrine much greater than B-HT 920 greater than or equal to methoxamine, and for the [3H]yohimbine binding sites, the order was clonidine greater than naphazoline greater than B-HT 920 greater than UK-14,304 greater than phenylephrine much greater than methoxamine. Similar pA2 values for prazosin and yohimbine were calculated regardless of whether alpha 1-selective agonist, methoxamine, or alpha 2-selective agonist, B-HT 920 were used. Putative alpha 2-adrenoceptor-selective agonists behave as partial agonists in functional studies inhibiting just maximal responses to alpha 1-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 alpha-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 alpha-adrenoceptor as a macromolecule has been proposed.
Agrawal
D K
DK
Daniel
E E
EE
D000316:Adrenergic alpha-Agonists / Q000145:classification / Q000378:metabolism*; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D015016:Yohimbine / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D011224:Prazosin