Coruzzi G, Poli E, Bertaccini G
Pharmacology. 1986;33(4):206-16. doi: 10.1159/000138218.
The contractile effect of the dihydropyridine analogue Bay K 8644, recently described as a Ca2+-agonist, has been evaluated in the rat isolated duodenal muscle in comparison with that of acetylcholine. Bay K 8644 (3 X 10(-10)-10(-6) mol/l) increased the duodenal motility, whereas it behaved as an inhibitor when tested at high concentrations (greater than 10(-6) mol/l). Bay K 8644 was more potent than acetylcholine (threshold concentration 3 X 10(-10) vs. 10(-8) mol/l) but less efficient. The contractile responses to Bay K 8644 and acetylcholine were reduced in calcium-free medium and abolished by addition of 1 mmol/l EGTA. In some K+-depolarized tissues, however, a contractile response to Bay K 8644 was still observed. The effects of Bay K 8644 and acetylcholine were antagonized by nifedipine and verapamil; however, a competitive antagonism was observed only for the interaction Bay K 8644-nifedipine (pA2 = 9.86). The contraction induced by Bay K 8644 was noncompetitively antagonized by low concentrations of atropine (10(-7) mol/l); Bay K 8644 (10(-7) mol/l) did not modify the response to acetylcholine, while inhibiting it at higher concentration (10(-5) mol/l); in addition, it was able to enhance the response to endogenous acetylcholine, released by field stimulation. The above results indicated that Bay K 8644 and cholinergic stimuli are strong activators of the duodenal motility in vitro. The interference of Bay K 8644 with the cholinergic system, observed in both unstimulated and electrically stimulated strips, suggested a novel site of action of this compound in the gastrointestinal muscle.
最近被描述为一种钙离子激动剂的二氢吡啶类似物Bay K 8644的收缩效应，已在大鼠离体十二指肠肌中与乙酰胆碱的收缩效应进行了比较评估。Bay K 8644（3×10⁻¹⁰ - 10⁻⁶mol/L）可增加十二指肠运动性，而在高浓度（大于10⁻⁶mol/L）测试时其表现为抑制剂。Bay K 8644比乙酰胆碱更有效力（阈浓度3×10⁻¹⁰对10⁻⁸mol/L）但效能较低。在无钙培养基中，对Bay K 8644和乙酰胆碱的收缩反应减弱，并通过添加1mmol/L乙二醇双四乙酸（EGTA）而消除。然而，在一些钾离子去极化的组织中，仍观察到对Bay K 8644的收缩反应。Bay K 8644和乙酰胆碱的效应被硝苯地平和维拉帕米拮抗；然而，仅在Bay K 8644 - 硝苯地平相互作用中观察到竞争性拮抗（pA2 = 9.86）。低浓度阿托品（10⁻⁷mol/L）对Bay K 8644诱导的收缩产生非竞争性拮抗作用；Bay K 8644（10⁻⁷mol/L）不改变对乙酰胆碱的反应，而在较高浓度（10⁻⁵mol/L）时抑制该反应；此外，它能够增强由场刺激释放的内源性乙酰胆碱的反应。上述结果表明，Bay K 8644和胆碱能刺激物是体外十二指肠运动性的强激活剂。在未刺激和电刺激的肠条中均观察到Bay K 8644对胆碱能系统的干扰，提示该化合物在胃肠肌中有一个新的作用位点。
