Effects of cocaine on a hypogastric nerve-vas deferens preparation of the guinea pig.

Abstract

Effects of cocaine on a hypogastric nerve-vas deferens preparation of the guinea pig, in vitro, were investigated with the microelectrode and the double sucrose gap methods. 1) Cocaine, at a concentration of more than 3 X 10 minus-5 M, depolarized the membrane and enhanced the electrical activity of the postjunctional membrane. These effects were, however, not due to accumulated noradrenaline near the postjunctional membrane. 2) The electrical resistance of the postjunctional membrane was slightly increased by treatment with cocaine (3 X 10 minus-5M) but the length constant of the tissue was almost unaffected. The electrical threshold to evoke a spike from the postjunctional membrane was lowered. 3) Cocaine (3 X 10 minus-5M) did not change the amplitude and frequency of the miniature excitatory junction potentials but it markedly suppressed the amplitude of the excitatory junction potentials evoked by hypogastric nerve stimulation. Cocaine prolonged the falling phase of the excitatory junction potentials. 4) The inhibitory action of cocaine on the junction potential evoked by nerve stimulation was not specific for the adrenergic fiber. Cocaine also suppressed the amplitude of the non-adrenergic inhibitory junction potential evoked in the taenia coli by field stimulation. 5) Exogeneously applied noradrenaline enhanced the electrical and mechanical activities of the postjunctional organ but suppressed the amplitude of the excitatory junction potential. This effect of noradrenaline was still observed on pretreatment with cocaine. 6) In the presence of cocaine, the dose-response curves plotted from the mechanical activity induced by excess [K]o or by noradrenaline shifted to the left and the maximum responses evoked by either treatment were enhanced. 7) From the present experiments, it was concluded that supersensitivity induced by cocaine or cocaine potentiation of the mechanical response may be mainly due to direct action on the smooth muscle tissue rather than to inhibition of noradrenaline re-uptake into the nerve terminals.