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 microM) and verapamil (1-100 microM) potentiated twitches maximally by about 1000% (EC50 17.3 nM) and 300% (EC50 17.5 microM), respectively. Nifedipine (0.1 nM-1 microM) only reduced twitch magnitude (IC50 7.7 nM). All effects were reversed following washout. 3. Yohimbine (1-100 microM) reversed twitch potentiation caused by verapamil but not by Bay K 8644. Prazosin (1 microM) 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 microM), but Bay K 8644 (1 microM) shifted the curve to nifedipine 120 fold to the right. Previous incubation with nifedipine (1 microM) blocked potentiation induced by verapamil but did not modify responsiveness to Bay K 8644. 5. Previous addition of verapamil (30 microM) 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 nM) 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).
Rae
G A
GA
Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Calixto
J B
JB
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*; D014649:Vas Deferens / Q000187:drug effects / Q000294:innervation; D014700:Verapamil / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D015016:Yohimbine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D009543:Nifedipine; D009638:Norepinephrine