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Abstract

Characterization of alpha-adrenergic receptor subtypes in the rat renal cortex. Differential regulation of alpha 1- and alpha 2-adrenergic receptors by guanyl nucleotides and Na.

M D Snavely and P A Insel
Molecular Pharmacology November 1982, 22 (3) 532-546;
M D Snavely
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P A Insel
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Abstract

We have used the subtype-selective radioligands [3H]prazosin (an alpha 1-adrenergic antagonist) and [3H]yohimbine (an alpha 2-adrenergic antagonist) to examine alpha-adrenergic receptors in rat renal cortical membranes. Under the conditions used in this study, [3H]prazosin bound only to alpha 1-adrenergic receptors, whereas [3H]yohimbine bound only to alpha 2-adrenergic receptors; the two radioligands were completely selective and did not bind to a common site. The ratio of alpha 2- to alpha 1-adrenergic receptors was about 3:1. Guanyl nucleotides decreased the affinity of epinephrine at both receptor subtypes, but this effect was greater at the alpha 2-receptor and, according to computer analysis, occurred through different mechanisms at the two receptor subtypes. NaCl decreased the affinity of epinephrine at both alpha-receptor subtypes; this effect was more Na+-selective at alpha 2- than at alpha 1-receptors. Guanyl nucleotides and NaCl were additive in decreasing the affinity of epinephrine at the alpha 1-receptor but were synergistic at the alpha 2-receptor. In addition, NaCl increased specific binding of [3H] yohimbine but had no effect on the binding of [3H]prazosin. This enhancement of [3H] yohimbine binding was Na+-specific and fully reversible, and represented an increase in maximal binding capacity. Although binding of epinephrine to both alpha 1- and alpha 2-receptors could be modulated by guanyl nucleotides, we were unable to detect inhibition by epinephrine of basal or hormone-stimulated adenylate cyclase activity. Thus, separate alpha 1- and alpha 2-adrenergic receptors can be detected in the rat renal cortex and binding to both receptor subtypes can be regulated by guanyl nucleotides and Na+ X Na+ may directly interact with alpha 2- but not alpha 1-adrenergic receptors in the renal cortex. Our findings with renal cortical membranes indicate that regulation of agonist binding at alpha-adrenergic receptor subtypes by guanyl nucleotides and Na+ is not limited to alpha 2-adrenergic receptors, as previously reported with other tissues.

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Molecular Pharmacology
Vol. 22, Issue 3
1 Nov 1982
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Abstract

Characterization of alpha-adrenergic receptor subtypes in the rat renal cortex. Differential regulation of alpha 1- and alpha 2-adrenergic receptors by guanyl nucleotides and Na.

M D Snavely and P A Insel
Molecular Pharmacology November 1, 1982, 22 (3) 532-546;

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Abstract

Characterization of alpha-adrenergic receptor subtypes in the rat renal cortex. Differential regulation of alpha 1- and alpha 2-adrenergic receptors by guanyl nucleotides and Na.

M D Snavely and P A Insel
Molecular Pharmacology November 1, 1982, 22 (3) 532-546;
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