EFFECTS OF THE MUSCARINIC AGONIST McN‐A‐343 ON THE RELEASE BY SYMPATHETIC NERVE STIMULATION OF [3H]‐NORADRENALINE FROM RABBIT ISOLATED EAR ARTERIES AND GUINEA‐PIG ATRIA

Abstract

1 McN-A-343 (4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride) in concentrations of 10⁻⁵ and 10⁻⁴ m inhibits the stimulation-induced efflux of radioactivity from segments of rabbit ear artery that have previously been incubated with (–)-[³H]-noradrenaline, and also decreases the contractile response. 2 The inhibitory effects of McN-A-343 (10⁻⁵ m) on the efflux of radioactivity and the contractions induced by low frequencies of stimulation (2 and 5 Hz) are reversed by atropine, but atropine does not modify these effects with high frequencies of stimulation (20 and 50 Hz). 3 McN-A-343 (10⁻⁴ m) enhances the stimulation-induced efflux of radioactivity from guinea-pig atria that have previously been incubated with (–)-[³H]-noradrenaline, and prolongs the positive inotropic response. These effects are not modified by atropine. 4 It is concluded that McN-A-343 has different effects on adrenergic transmitter release in the two tissues. In the artery, it acts as an agonist on muscarinic receptors of adrenergic terminals to inhibit transmitter release at low frequencies of stimulation. In the atria it enhances transmitter efflux from the tissue, largely by inhibiting re-uptake.