Interactions of calcium antagonists and the calcium channel agonist Bay K 8644 on neurotransmission of the mouse isolated vas deferens

1 The present study compares the effects of verapamil and Bay K 8644 on twitches of the mouse vas deferens induced by field stimulation at 0.1 Hz. The influence of interactions between these drugs and nifedipine on neurotransmission was also investigated. 2 Bay K 8644 (0.1 nm‐3 μ m ) and verapamil (1–100 μ m ) potentiated twitches maximally by about 1000% (EC 50 17.3 n m ) and 300% (EC 50 17.5 μ m ), respectively. Nifedipine (0.1 nM‐1μ m ) only reduced twitch magnitude (IC 50 7.7 n m ). All effects were reversed following washout. 3 Yohimbine (1–100 μ m ) reversed twitch potentiation caused by verapamil but not by Bay K 8644. Prazosin (1 μ m ) did not reduce basal twitch tension nor antagonize twitch potentiation by verapamil. 4 Twitch inhibition by nifedipine was unaltered by previous incubation with verapamil (30 μ m ), but Bay K 8644 (1 μ m ) shifted the curve to nifedipine 120 fold to the right. Previous incubation with nifedipine (1 μ m ) blocked potentiation induced by verapamil but did not modify responsiveness to Bay K 8644. 5 Previous addition of verapamil (30 μ m ) markedly enhanced twitch potentiation caused by Bay K 8644 in a supra‐additive fashion. In experiments conducted in the reversed condition, Bay K 8644 (1 nM but not 10 n m ) potentiated the effect of verapamil in a similar manner but to a lesser extent. 6 It is concluded that verapamil, in contrast to nifedipine, markedly enhances neurally‐evoked twitches of the mouse vas deferens. Bay K 8644 produces essentially the same effect as verapamil, but its potency is 1000 fold and its maximal effect about 3 fold greater than that observed for verapamil. It is suggested that the mechanism of twitch potentiation by verapamil is different from that of Bay K 8644 and may involve an increased release of non‐adrenergic co‐transmitter(s).