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

Devendra K. Agrawal, E. E. Daniel

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)S66-S75
JournalJournal of Cardiovascular Pharmacology
Volume7
StatePublished - 1985
Externally publishedYes

Fingerprint

Mesenteric Arteries
Adrenergic Receptors
Binding Sites
Yohimbine
Prazosin
Naphazoline
Methoxamine
Clonidine
Phenylephrine
Norepinephrine
Cell Membrane
talipexole

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

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title = "Agonists interaction with radiolabeled α-adrenoceptor antagonists binding sites in rat mesenteric artery",
abstract = "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.",
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