Presynaptic modulation of acetylcholine release from cardiac parasympathetic neurons

Abstract

Acetylcholine [ACh] can be released from parasympathetic nerve endings in rat atria by 56 mM K+ depolarization or by electrical field stimulation. The presynaptic modulation of ACh release from superfused rat atria prelabeled with [3H]choline was studied. Exogenous ACh and the specific muscarinic agonist oxotremorine inhibit the stimulation-induced overflow of [3H]ACh into the superfusion medium. The half-maximal inhibitory concentration (IC50) of oxotremorine is 0.3 .mu.M. The cholinesterase inhibitor neostigmine also decreases K+-stimulated [3H]ACh overflow, whereas the muscarinic antagonist atropine enhances the overflow of [3H]ACh. ACh release in atria is modulated through negative feedback by the endogenous transmitter. The sympathetic adrenergic neurotransmitter norepinephrine and the neurohormone epinephrine also inhibit the overflow of [3H]ACh by .apprx. 60%. The IC50 values for the inhibitory effects of these catecholamines are 6.3 and 2.2 .mu.M, respectively. The inhibitory effect of norepinephrine is blocked by the .alpha.-adrenergic receptor antagonist yohimbine but not by the .beta.-adrenergic receptor antagonist propranolol. Evidently, presynaptic muscarinic and .alpha.-adrenergic receptors participate in the physiological and pharmacological control of cardiac parasympathetic activity.