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Journal of Pharmacology And Experimental Therapeutics, Vol. 173, Issue 2, 416-421, 1970
Copyright © 1970 by American Society for Pharmacology and Experimental Therapeutics

ACETYLCHOLINE-INDUCED RELEASE OF NOREPINEPHRINE IN THE PRESENCE OF TETRODOTOXIN

KENNETH R. KRAUSS 1, DAVID O. CARPENTER 1, and IRWIN J. KOPIN 1

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

Intra-arterial administration of acetylcholine evokes release of norepinephrine from the isolated perfused cat spleen and induces antidromic nerve impulses in the splenic nerve. Addition of tetrodotoxin (0.1 mg/kg) to the perfusing solution prevents release of norepinephrine by splenic nerve stimulation and blocks the antidromic discharge produced by acetylcholine but does not abolish the catecholamine release induced by acetylcholine. Single doses of bretylium block release of norepinephrine produced by stimulation of the splenic nerve but not that produced by acetylcholine. Bretylium perfused in high concentrations blocks release of norepinephrine induced by acetylcholine in the tetrodotoxintreated spleen. These observations and those of others support the view that bretylium interferes with action potential-induced release of norepinephrine and antagonizes the effects of acetylcholine by a mechanism which does not involve interference with nerve impulse conduction.

Submitted on November 4, 1969
Accepted on February 27, 1970




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