Abstract

The influence of cocaine on the responses of the superfused rat vas deferens to norepinephrine (NE), tyramine, Ba⁺⁺, Ca⁺⁺, K⁺ and transmural stimulation was examined. Enhanced responses of the vasa deferentia to NE, Ba⁺⁺, Ca⁺⁺, K⁺ and transmural stimulation were observed with doses of cocaine (1, 3 and 10 µg/ml) which reduced the responses of the vasa deferentia to tyramine. Tetrodotoxin (0.1 µg/ml) and propranolol (1 µg/ml) did not affect cocaine-induced potentiation of the responses of the vasa deferentia to any agonist. Reserpine (5.0 mg/kg) 48 and 24 hours prior to sacrifice and bretylium (20 µg/ml) and guanethidine (20 µg/ml) antagonized cocaine-induced potentiation of the responses of the vasa deferentia to K⁺, Ba⁺⁺ and Ca⁺⁺. These antiadrenergic agents blocked the responses to tyramine but did not alter cocaineinduced potentiation of the responses to NE. When Ca⁺⁺ was removed from the superfusate the responses of the vasa deferentia to Ba⁺⁺ and Ca⁺⁺ were facilitated by cocaine. All pharmacologic interventions failed to antagonize cocaine-induced potentiation of the maximum response of the vasa deferentia to NE. These findings support the conclusions that the enhanced responses of the vasa deferentia to ionic stimulants are mediated by the presynaptic inhibition of NE uptake by cocaine. A second mechanism of cocaine action appears to involve alteration of muscle permeability to calcium ions or an increase in the amount of calcium ion available for muscle contraction.