GANGLIONIC ACTIONS OF MUSCARINIC SUBSTANCES

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

Intraarterial injections of McN-A-343 and AHR-602 into the blood supply of the nonatropinized, nonperfused superior cervical ganglion of the spinal cat caused contraction of the nictitating membrane in all preparations. Similar injections of small amounts of muscarine caused a response of the nictitating membrane in 19 out of 36 preparations. Chronically denervated ganglia were supersensitive to all three substances, and muscarine caused a response in all denervated preparations.

Responses of the nictitating membrane following intraarterial injections of muscarine, McN-A-343 amid AHR-602 to the ganglion were due to stimulation of the ganglion by these agents: destruction of the ganglion abolished the response, and all three agents were ineffective when injected during ganglion block by depolarization produced by TMA or nicotine. During the phase of "non-depolarizing ganglion block by nicotine" muscarine, McX-A-343 and AHR-602 were able to stimulate the ganglion at a time when DMPP and nicotine produced no response.

The ganglionic response to muscarine, McN-A-343 and AHR-602 was not blocked by hexamethonium but was antagonized by small amounts of atropine. Cocaine, morphine and methadone severely reduced the response of the ganglion to muscarinic substances but were ineffective against nicotine, DMPP, KCl and preganglionic stimulation.

Subthreshold amounts of McN-A-343, AHR-602 and muscarine were found to facilitate submaximal, preganglionic stimulation. It was also observed that supramaximal, preganglionic stimulation often potentiated the response of the ganglion to these three substances.

Muscarine, McN-A-343 and AHR-602 are similar to pilocarpine in their ganglion-stimulating properties, and all four agents stimulate ganglia by an action on a muscarinic receptor which differs from the nicotinic receptor. On the basis of the results of this work and those obtained by other investigators, it is suggested that the attachment of endogenous acetylcholine to muscarinic receptors at the ganglion cell may serve to modify the normal ganglionic transmission initiated by an action of acetylcholine on the nicotinic receptors.