ACTIONS OF ANTICHOLINESTERASE AGENTS UPON GANGLIONIC TRANSMISSION IN THE DOG

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

The effect of anticholinesterase agents on impulse transmission in cardiac sympathetic ganglia was studied in open-chest, spinal dogs. The right preganglionic trunk was stimulated supramaximally at increasing frequencies; heart rate was used as indicator. Physostigmine (0.2-0.3 mg/kg) or diisopropylfluorophosphate (0.5-2 mg/kg) did not affect the resting heart rate when given slowly in divided doses. Conditions of pure nicotinic or pure muscarinic transmission were produced by administration of supramaximal doses of either atropine or nicotinic blocking agents (hexamethonium, nicotine, mecamylamine and chlorisondamine) respectively. The anticholinesterase agents did not potentiate transmission under nicotinic conditions with submaximal stimulation or even when partial block by hexamethonium or mecamylamine was produced. In contrast, the same doses of anticholinesterase agents shifted the frequency-response curve to the left when transmission was muscarinic. Antagonism to complete block produced by nicotinic agents plus small doses of atropine could also be shown and was blocked by subsequent larger doses of atropine. Transmission depressed after hemicholinium-3 was restored by anticholinesterase agents under muscarinic but not under nicotinic conditions. The different effects of the anticholinesterases under the two conditions are interpreted as evidence for a different role of cholinesterase in impulse transmission under these conditions.