Abstract

Dose-response curves of acetylcholine were obtained by means of intraarterial injections of this substance into the blood supply of the nictitating membrane of the spinal cat. The mode of action of acetylcholine was analyzed by determining changes in the dose-response curve after the administration of various substances known to reduce or abolish time response of the nictitating membrane to nerve stimulation, tyramine or norepinephrine. Intravenous injections of 2,6-xylyl choline ether bromide (TM 10) or pretreatment of the animals with maximally tolerated doses of reserpine failed to alter the response to acetylcholine, whereas the intravenous injection of 10 mg/kg phenoxybenzamine slightly reduced it. It is therefore higlmly unlikely that acetylcholine acts through the release of endogenous norepinephrine.

Cocaine increases the response of the nictitating membrane to small amounts of acetylcholine but not that to large amounts. Cocaine fails to increase the response to acetylchohine after pretreatment with maximally tolerated doses of reserpine. These observations do not support the hypothesis that cocaine causes supersensitivity of the nictitating membrane to acetyleholine. They are consistent with the view that this "potentiation" is an additive synergism of endogenous norepinephrine with injected acetylcholine. Chronic postganglionic denervation, on the other hand, produces supersensitivity to acetylcholine.