An analysis of the effects of cocaine on the responsiveness of the isolated guinea pig vas deferens to noradrenaline and other agonists.

In the isolated guinea pig vas deferens, 10(-4) M cocaine shifts to the left (13.5-fold at the EC50 level) the concentration-effect curve and increases the maximum response to noradrenaline, whilst supersensitivity to phenylephrine, an amine with a low affinity for the neuronal uptake, was smaller (4.1-fold) and the maximum response was not increased. Cocaine did not enhance sensitivity and maximum response to acetylcholine, potassium and calcium. Supersensitivity to noradrenaline was caused by a decreased dissociation constant (Km) for the agonist-adrenoreceptor interaction without alteration of the tissue's maximum response (Rmax). pA2 and pD'2 values in the presence of cocaine were not significantly different from control which indicates that cocaine did not increase the affinity of adrenoreceptors for the sympathomimetic amines used. It is concluded that the supersensitivity of the isolated guinea pig vas deferens to noradrenaline and phenylephrine by cocaine is entirely of prejunctional origin and results from the blockade of the neuronal uptake process.