EFFECTS OF DRUGS ON ACETYLCHOLINE RELEASE FROM THE CAT SUPERIOR CERVICAL GANGLION BY CARBACHOL AND BY PREGANGLIONIC STIMULATION

¹ Department of Pharmacology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

The effects of muscarinic and nicotinic cholinergic blocking agents and other drugs were studied on the release of acetylcholine (ACh) from the cat superior cervical ganglion by carbachol (0.25-1.0 µg) and by preganglionic stimulation (10 cps, 0.5-msec duration, supramaximal voltage, for 3 min). Atropine (10.0 and 33.3 µg), hexamethonium (1 and 2 x 10-4 M), dihydro--erythroidine (3 x 10^-4 M) and diallyl-bis-nortoxiferine (3 x 10^-5 M) caused various degrees of reduction of ACh release in response to carbachol, but did not modify ACh release by preganglionic stimulation. Mecamylaminc (2 x 10^-4 M) and strychnine methiodide (50 µ/ml) were ineffective against either type of ACh release. No effect on ACh release by preganglionic stimulation was obtained by the combined administration of atropine with several nicotinic blocking agents. Procaine, at 50.0 and 10.0 µml, reduced ACh release by both preganglionic stimulation and carbacilol; at 1.0 µml, it reduced only carbachol-induced ACh release. In contrast, strychnine sulfate caused significant reduction of ACh release by preganglionic stimulation over the dose range of 100.0 to 1.0 µg/ml; carbachol-induced ACh release was not reduced significantly. The previous conclusion, that different primary mechanisms are involved in the release of ACh by preganglionic stimulation and by carbachol, is reaffirmed. It is proposed that strychnine may block selectively presynaptic cholinoreceptors, and that its blocking action at certain inhibitory pathways in the central nervous system may involve interference with ACh-mediated release of the inhibitory transmitter.