CHARACTERIZATION OF ALPHA-ADRENERGIC RECEPTOR SUBTYPES IN THE RAT RENAL CORTEX - DIFFERENTIAL REGULATION OF ALPHA-1-ADRENERGIC AND ALPHA-2-ADRENERGIC RECEPTORS BY GUANYL NUCLEOTIDES AND NA+

Abstract

The subtype-selective radioligands [3H]prazosin (an .alpha.1-adrenergic antagonist) and [3H]yohimbine (an .alpha.2-adrenergic antagonist) were used 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 2 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, occured through different mechanisms at the 2 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. 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, inhibition by epinephrine of basal or hormone-stimulated adenylate cyclase activity was not detected. 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+. Na+ may directly interact with .alpha.2- but not .alpha.1-adrenergic receptors in the renal cortex. Regulation of agonist binding at .alpha.2-adrenergic receptor subtypes by guanyl nucleotides and Na+ is evidently not limited to .alpha.2-adrenergic receptors, as previously reported with other tissues.