RENAL ALPHA-1 AND ALPHA-2 ADRENERGIC-RECEPTORS - BIOCHEMICAL AND PHARMACOLOGICAL CORRELATIONS

Abstract

[3H]Dihydroergocryptine, a nonselective .alpha.-adrenergic antagonist, the .alpha.-1 selective antagonist, [3H]prazosin and the .alpha.-2 selective antagonist, [3H]yohimbine, were used to study binding sites in rat renal membranes. To establish a correlation between binding and a biological function, the ability of .alpha.-adrenergic agents to stimulate or inhibit vasoconstriction was quantified in vitro using an isolated perfused kidney preparation. Binding with each radioligand was rapid, saturable and specific. The order of potencies of a variety of adrenergic agents, determined by competitive inhibition studies, suggested that the binding of each radioligand was to sites with .alpha.-adrenergic specificity. The total umber of binding sites in these rat renal membranes, determined with [3H]dihydroergocryptine (Bmax [maximum binding], 212 fmol/mg of protein; Kd, 12.8 nM) was approximately equal to the sum of binding site concentrations determined with the .alpha.-1 and .alpha.-2 selective radioligands (Bmax 57 and 170 fmol/mg of protein; Kd, 0.85 and 20 nM, respectively). The .alpha.-receptor mediating renal arteriolar vasoconstriction appeared to be of the .alpha.-1 subtype as there was a close correlation between the in vitro results and the binding data determined with [3H]prazosin (r = 0.93). In addition, in both the functional and [3H]prazosin binding studies, unlabeled prazosin was 5 to 40-fold more potent than the nonselective antagonist, phentolamine, and 400- to 1500-fold more potent than the .alpha.-2 antagonist, yohimbine. Rat renal plasma membranes probably contain binding sites with both .alpha.-1 and .alpha.-2 adrenergic receptor specificity, in a ratio of approximately 1:3. Despite the preponderance of .alpha.-2 receptors, the .alpha.-receptor mediating renal vasoconstriction appears to be of the .alpha.-1 type.