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).
摘要
本研究比较了维拉帕米和Bay K 8644对0.1 Hz场刺激诱导的小鼠输精管抽搐的影响。还研究了这些药物与硝苯地平之间的相互作用对神经传递的影响。2. Bay K 8644（0.1 nM - 3 microM）和维拉帕米（1 - 100 microM）分别使抽搐最大增强约1000%（EC50 17.3 nM）和300%（EC50 17.5 microM）。硝苯地平（0.1 nM - 1 microM）仅降低抽搐幅度（IC50 7.7 nM）。冲洗后所有效应均逆转。3. 育亨宾（1 - 100 microM）可逆转维拉帕米引起的抽搐增强，但不能逆转Bay K 8644引起的增强。哌唑嗪（1 microM）既不降低基础抽搐张力，也不拮抗维拉帕米引起的抽搐增强。4. 硝苯地平引起的抽搐抑制不受预先用维拉帕米（30 microM）孵育的影响，但Bay K 8644（1 microM）使硝苯地平的曲线右移120倍。预先用硝苯地平（1 microM）孵育可阻断维拉帕米诱导的增强，但不改变对Bay K 8644的反应性。5. 预先加入维拉帕米（30 microM）以超相加方式显著增强Bay K 8644引起的抽搐增强。在相反条件下进行的实验中，Bay K 8644（1 nM而非10 nM）以类似方式增强维拉帕米的作用，但程度较小。6. 得出结论，与硝苯地平相反，维拉帕米显著增强小鼠输精管神经诱发的抽搐。Bay K 8644产生与维拉帕米基本相同的作用，但其效力比维拉帕米高1000倍，最大效应比维拉帕米大约3倍。提示维拉帕米增强抽搐的机制与Bay K 8644不同，可能涉及非肾上腺素能共递质释放增加。
