MODIFICATION OF GANGLIONIC RESPONSES TO CHOLINOMIMETIC DRUGS FOLLOWING PREGANGLIONIC STIMULATION, ANTICHOLINESTERASE AGENTS AND PILOCARPINE

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

An analysis was made of the alterations in the responses to drugs produced by repetitive stimulation of the preganglionic nerve of the superior cervical ganglia of cats. A sustained, low amplitude depolarization of the ganglia, which was sensitive to blockade by atropine, was observed following repetitive preganghionic stimulation, the administration of anticholinesterase agents, and the injection of pilocarpine. Marked changes in the ganglionic responses to acetylcholine (ACh) and methacholine (MCh) occurred when the choline esters were administered during the depolarization evoked by the above procedures.

The initial period of depolarization produced by ACh (D potential) was depressed after preganglionic stimulation at a time when the "early" postganglionic response (ER) to ACh was enhanced. Similar results were obtained in ganglia treated with large doses of anticholinesterase agents or pilocarpine. Small doses of atropine prevented the depression of the D potential but had no effect on the ER to ACh. The ganghionic hyperpolarization (H potential) evoked by ACh or MCh was enhanced in hanglia conditioned by preganglionic stimulation, the anticholinesterase agents, or piocarpine. On the other hand, the late occurring depolarization (LD potential) evoked by ACh or MCh was depressed under these conditions. The "late" postganglionic response (LR) to ACh and MCh was enhanced by the anticholinesterase agents and preganglionic stimulation but not by pilocarpine. Atropine blocked the H and LD potentials and the LR to the choline esters.

Although the findings demonstrate a parallelism between depolarization of atropine-sensitive cholinoceptive sites and enhanced postganglionic responses to ganglionic stimulating agents, the failure of atropine to prevent the development by preganglionic stimulation of enhanced responses to ACh argues against a cause and effect relationship. The alterations occurring in conditioned ganglia of the contours of the ganglionic potentials evoked by ACh and MCh are explained provisionally on the basis of persistent ganglionic depolarization of atropine-sensitive sites.

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