Acetylcholine release from rat atria can be regulated through an α1-adrenergic receptor

Abstract

Isolated superfused rat atria release [3H]acetylcholine when depolarized with 57 mM potassium. The depolarization-induced overflow of [3H]acetylcholine is markedly inhibited by micromolar concentrations of epinephrine and norepinephrine. The α1-selective adrenergic agonist methoxamine also inhibits tritium overflow, but the α2-selective adrenergic agonist clonidine and the β2-adrenergic agonist isoproterenol do not. Prazosin, an selective α1-adrenergic antagonist, blocks adrenergic inhibition of [3H]acetylcholine overflow with a K(i) of approximately 0.4 nM. Yohimbine has approximately one-hundredth the potency of prazosin for blocking adrenergic inhibition of [3H]acetylcholine overflow. [3H]Norepinephrine overflow from isolated rat atria is also inhibited by norepinephrine, but this effect is antagonized by yohimbine and not by prazosin. We suggest that the release of acetylcholine from cardiac parasympathetic neurons can be regulated through an α1-adrenergic receptor, and that this mechanism may underly, at least in part, the relative lack of effects of prazosin on heart rate.