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 language | English |
|---|---|
| Pages (from-to) | S66-S75 |
| Journal | Journal of Cardiovascular Pharmacology |
| Volume | 7 |
| State | Published - 1985 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine
- Pharmacology
Cite this
Agonists interaction with radiolabeled α-adrenoceptor antagonists binding sites in rat mesenteric artery. / Agrawal, Devendra K.; Daniel, E. E.
In: Journal of Cardiovascular Pharmacology, Vol. 7, 1985, p. S66-S75.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Agonists interaction with radiolabeled α-adrenoceptor antagonists binding sites in rat mesenteric artery
AU - Agrawal, Devendra K.
AU - Daniel, E. E.
PY - 1985
Y1 - 1985
N2 - 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.
AB - 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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M3 - Article
VL - 7
SP - S66-S75
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
SN - 0160-2446
ER -