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Effects of cocaine on the isotonic contractions of isolated vas deferens of intact and reserpinized guinea pigs to acetylcholine were examined. Both cocaine-induced increase in sensitivity to acetylcholine and cocaine-induced increase in maximum response of Ca2+-contraction was attenuated remarkably by reserpine. However, cocaine-induced increases in acetylcholine- and K+-contractions in Ca2+-free Tyrode solution were not prevented by reserpine. Acetylcholine-contraction, but not K+-contraction, in the preparation exposed for 5 min to Ca2+-free Tyrode solution were inhibited by reserpine. Cocaine did not inhibit the cholinesterase activity of vas deferens of guinea pig. These results suggested that presynaptic mechanisms of cocaine-induced supersensitivity are excluded and that inhibitory effect of reserpine on cocaine-induced supersensitivity might be due to the inhibition of cocaine-induced increase in calcium-influx into smooth muscle cells of vas deferens.

journal of pharmacobio-dynamics

Pharmacological studies on supersensitization. VIII. Dissociation of induction of supersensitivity from presynaptic action of cocaine on isolated vas deferens of guinea pig.