Dong De-Li, Wang Qing-Hui, Chen Wei, Fan Jiao-Jie, Mu Jing-Wei, Ke Jia, Yang Bao-Feng
Department of Pharmacology, Harbin Medical University; Bio-pharmaceutical Key Laboratory, Baojian Road 157, Harbin 150086, Heilongjiang Province, China.
Eur J Pharmacol. 2005 Feb 21;509(2-3):179-85. doi: 10.1016/j.ejphar.2005.01.013.
Many different K+ channels have been identified in the gastrointestinal tract, and the two classical K+ channel blockers, tetraethylammonium and 4-aminopyridine, show different sensitivity for these channels. The aim of the present study was to compare the effects of tetraethylammonium and 4-aminopyridine on the gastrointestinal function of mice. 4-Aminopyridine (5 mg/kg, p.o.) inhibited, but tetraethylammonium (40 mg/kg, p.o.) enhanced, the intestinal propulsion of a charcoal suspension in conscious mice. Studies in vitro showed that perfusion of 5 mM 4-aminopyridine increased the maximal contractile force and minimal relaxation force, and decreased the amplitude and frequency of the peristaltic contraction of the isolated duodenum. However, perfusion of 5 mM tetraethylammonium increased the maximal contractile force, the minimal relaxation force and the amplitude of the contraction. The effects of tetraethylammonium and 4-aminopyridine on the duodenal contraction could be abolished completely by application of 5 microM verapamil. Our results in vivo and in vitro showed that tetraethylammonium and 4-aminopyridine had contrasting effects on the gastrointestinal function of mice.
在胃肠道中已鉴定出许多不同的钾离子通道,两种经典的钾离子通道阻滞剂,四乙铵和4-氨基吡啶,对这些通道表现出不同的敏感性。本研究的目的是比较四乙铵和4-氨基吡啶对小鼠胃肠功能的影响。4-氨基吡啶(5毫克/千克,口服)抑制清醒小鼠中炭悬浮液的肠道推进,而四乙铵(40毫克/千克,口服)则增强其推进。体外研究表明,灌注5毫摩尔/升的4-氨基吡啶可增加离体十二指肠最大收缩力和最小舒张力,并降低蠕动收缩的幅度和频率。然而,灌注5毫摩尔/升的四乙铵可增加最大收缩力、最小舒张力和收缩幅度。应用5微摩尔/升维拉帕米可完全消除四乙铵和4-氨基吡啶对十二指肠收缩的影响。我们的体内和体外研究结果表明,四乙铵和4-氨基吡啶对小鼠胃肠功能具有相反的作用。