Selective inhibitory effects of calcium channel antagonists on the two components of the neurogenic response of guinea pig vas deferens.

The effects of L-type calcium channel antagonists and omega-conotoxin on the contractile responses of guinea pig vas deferens were examined in vitro. Electrical stimulation of the postganglionic hypogastric nerve induced biphasic contraction consisting of rapid phasic and delayed tonic components. L-type calcium channel antagonists, such as diltiazem, verapamil and nicardipine, mainly inhibited the delayed tonic component, whereas omega-conotoxin mainly inhibited the rapid phasic component. Stimulations in the presence of prazosin and alpha, beta-methylene ATP induced rapid transient and delayed contraction, respectively, which were inhibited by omega-conotoxin and L-type calcium channel antagonists, respectively. Short-term stimulation with five pulses induced a small fast phasic contraction. This contraction, which could be desensitized by alpha, beta-methylene ATP, was inhibited by omega-conotoxin, but not by L-type calcium channel antagonists. At the concentrations used in the present study, none of the calcium channel antagonists inhibited the contractions induced by exogenously added ATP or norepinephrine. These findings suggest that L-type calcium channel antagonists and omega-conotoxin inhibit the neurotransmissions mediated by norepinephrine and ATP, respectively, from the postganglionic nerve to the vas deferens of the guinea pig. Inhibition of the voltage-dependent calcium channel is discussed in relation to the mechanism of cotransmission in this preparation.