Аннотация:In mammalian myocardium acetylcholine (ACh), which represents the main neurotransmitter of cardiac parasympathetic postganglionic fibers, can be released both via quantal (vesicular) and non-quantal (non-vesicular) mechanism of secretion. Non-quantal release is continuous, independent on vagus activity and exocytosis of ACh-containing vesicles. During the incubation of myocardium in the presence of acetylcholinesterase (AChE) inhibitors non-quantal ACh release leads to accumulation of ACh in myocardium and cholinergic effects, which are proportional to the intensity of non-quantal secretion. The aim of the present study was to reveal if non-quantal release of ACh can be modulated by another major cardioregulator norepinephrine or represents just uncontrolled leakage of ACh from cholinergic fibers. Cholinergic changes of electrical activity induced by AChE inhibitor paraoxon (5×10-6M) in isolated rat right atrial preparations were determined by means of standard microlectrode technique and used as a measure of non-quantal release intensity. Norepinephrine (10-7М and 10-6М), substantially suppressed, but not abolished, effects of paraoxon via stimulation of α-adrenoreceptors, since all experiments were conducted in the presence of β-blocker propranolol (5×10-6M). Blocker of ganglionic transmission hexamethonium bromide (10-4M) failed to alter the inhibitory effect of norepinephrine, indicating that only non-quantal ACh release is suppressed by this neurotransmitter. Effects of norepinephrine could be reduced by α2-antagonist yohimbine (10-6M). However, both α1-agonist phenylephrine (10-6M) and α2-agonist clonidine (10-6M) significantly inhibited cholinergic effects of paraoxon indicating the possible involvement of both α-receptor subtypes in mediation of adrenergic inhibition of non-quantal ACh release. Thus, cardiac non-quantal ACh release can be negatively regulated by norepinephrine providing another facet of sympathetic-parasympathetic interaction in the heart.