Interaction of amiloride with α-adrenoreceptors: evidence from radioligand binding studies

Abstract

We investigated the effect of amiloride on α-adrenoreceptors (α1 and α2) using radioligand binding techniques. Amiloride inhibited [3H]yohimbine and [3H]prazosin binding to α2- and α1-adrenoreceptors, respectively, from various tissues in a concentration-dependent manner. Amiloride was approximately 9–12 times more potent in inhibiting [3H]yohimbine binding to α2-adrenoreceptors from rat tissues than from other mammalian tissues. However, it had almost the same potency in inhibiting [3H]prazosin binding to α1-adrenoreceptors from rat as well as other mammalian tissues. Further, in rat tissues, amiloride was approximately 10 times more potent in inhibiting [3H]yohimbine than [3H]prazosin binding. Amiloride inhibited [3H]yohimbine binding noncompetitively and [3H]prazosin binding competitively. The inhibition of [3H]yohimbine and [3H]prazosin binding by amiloride was reversible. Since amiloride has been shown to be an inhibitor of Na+–H+ exchanger protein, we believe that it regulates the α2-adrenoreceptors by binding to Na+–H+ exchanger protein. Triamterene, a compound similar to amiloride in regard to diuretic effect, had very little effect on [3H]yohimbine and [3H]prazosin binding to rat kidney membranes, suggesting that the α-adrenoreceptor antagonistic properties of amiloride are not related to its antikaliuretic effect. The results of the present study suggest that some of the pharmacological actions of amiloride (antihypertensive and diuretic effects) can be explained in part by its regulatory effect on both α1- and α2-adrenoreceptors.