INTERACTIONS OF BRETYLIUM AND ACETYLCHOLINE AT SYMPATHETIC NERVE ENDINGS

¹ Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland

Tritiated bretylium, which is retained in the heart and spleen of cats for 1 day after its intramuscular or intraperitoneal injection, can be released by sympathetic nerve stimulation. Bretylium is not released by acetylcholine, although norepinephrine is released by acetylcholine as well as by sympathetic nerve stimulation. There are a number of differences between bretylium and norepinephrine which indicate that the drug does not replace norepinephrine. Bretylium, in low concentrations, blocks the release of norepinephrine by nerve stimulation, but does not block the effects of acetylcholine. It is concluded that the site of action of bretylium is anatomically or functionally proximal to the site at which acetylcholine acts in releasing norepinephrine from the sympathetic nerve. Bretylium may act by replacing a cholinergic link in the sequence of events leading to transmitter release which occurs when a sympathetic nerve impulse arrives at the nerve ending.