Fovaeus M, Andersson K E, Batra S, Morgan E, Sjögren C
J Urol. 1987 Apr;137(4):798-803. doi: 10.1016/s0022-5347(17)44214-5.
In isolated bladder smooth muscle from both rabbit and man, carbachol-induced contractions were reduced by the calcium channel blocker nifedipine, whereas the calcium channel promotor Bay K 8644 had no effect. In nominally calcium-free medium containing 10(-4) M EGTA, carbachol-induced contractions were reduced by 69% (rabbit) and 87% (man). These contractions were abolished by nifedipine, whereas Bay K 8644 significantly increased their amplitude, in rabbit preparations almost to control level. Electrical field stimulation produced contractions which could be suppressed by scopolamine by about 50% (rabbit) and more than 90% (man). These contractions were abolished by calcium-free medium (10(-4) M EGTA), suppressed by nifedipine, but significantly enhanced by Bay K 8644. The depressant effects of nifedipine, verapamil and diltiazem were reversed by Bay K 8644. The calcium channel blockers relaxed K+-induced contractions to base line, and this action was counteracted by Bay K 8644, less effectively when relaxations were induced by diltiazem. It is concluded that contractions produced by muscarinic receptor stimulation are primarily dependent on calcium bound to the outside of the membrane of the smooth muscle, and/or coming from the extracellular medium. Electrically evoked, scopolamine sensitive contractions seem to be mediated by a mechanism different from that of contractions produced by exogenously added muscarinic receptor agonist. The present data support the view that combined blockade of muscarinic receptors and calcium channels is an effective way of inhibiting bladder contractions in both rabbit and man.
在兔和人的离体膀胱平滑肌中，钙通道阻滞剂硝苯地平可减弱卡巴胆碱诱导的收缩，而钙通道促进剂Bay K 8644则无此作用。在含有10⁻⁴ M乙二醇双四乙酸（EGTA）的无钙名义培养基中，卡巴胆碱诱导的收缩在兔中减少了69%，在人中减少了87%。这些收缩被硝苯地平消除，而Bay K 8644则显著增加其幅度，在兔的标本中几乎恢复到对照水平。电场刺激产生的收缩可被东莨菪碱抑制约50%（兔）和超过90%（人）。这些收缩被无钙培养基（10⁻⁴ M EGTA）消除，被硝苯地平抑制，但被Bay K 8644显著增强。Bay K 8644可逆转硝苯地平、维拉帕米和地尔硫䓬的抑制作用。钙通道阻滞剂可使钾离子诱导的收缩松弛至基线，而Bay K 8644可抵消这一作用，地尔硫䓬诱导松弛时效果较差。结论是，毒蕈碱受体刺激产生的收缩主要依赖于结合在平滑肌细胞膜外侧的钙和/或来自细胞外介质的钙。电诱发的、对东莨菪碱敏感的收缩似乎是由一种不同于外源性添加毒蕈碱受体激动剂产生收缩的机制介导的。目前的数据支持这样一种观点，即联合阻断毒蕈碱受体和钙通道是抑制兔和人膀胱收缩的有效方法。
