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

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.