Shimada T, Kurachi Y, Terano A, Hamada E, Sugimoto T
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Gastroenterol Jpn. 1990 Apr;25(2):175-9. doi: 10.1007/BF02776812.
We examined effects of trimebutine maleate on the membrane currents of the intestinal smooth muscle cells by using the tight-seal whole cell clamp technique. Trimebutine suppressed the Ba2+ inward current through voltage-dependent Ca2+ channels in a dose-dependent manner. The inhibitory effect of trimebutine on the Ba2+ inward current was not use-dependent. It shifted the steady-state inactivation curve to the left along the voltage axis. Trimebutine also had inhibitory effects on the other membrane currents of the cells, such as the voltage-dependent K+ current, the Ca2(+)-activated oscillating K+ current and the acetylcholine-induced inward current. These relatively non-specific inhibitory effects of trimebutine on the membrane currents may explain, at least in part, the dual actions of the drug on the intestinal smooth muscle contractility, i.e. inhibitory as well as excitatory.
我们采用全细胞膜片钳技术，研究了马来酸曲美布汀对肠道平滑肌细胞膜电流的影响。曲美布汀以剂量依赖的方式抑制通过电压依赖性钙通道的Ba2+内向电流。曲美布汀对Ba2+内向电流的抑制作用不具有使用依赖性。它使稳态失活曲线沿电压轴向左移动。曲美布汀对细胞的其他膜电流也有抑制作用，如电压依赖性钾电流、Ca2(+)-激活的振荡钾电流和乙酰胆碱诱导的内向电流。曲美布汀对膜电流的这些相对非特异性的抑制作用可能至少部分解释了该药物对肠道平滑肌收缩性的双重作用，即抑制和兴奋作用。
