洛哌丁胺对豚鼠胆囊上皮的纳洛酮不敏感转运作用。

Naloxone-insensitive transport effects of loperamide in guinea-pig gallbladder epithelium.

作者信息

Wehner F, Winterhager J M, Petersen K U

机构信息

Institut für Pharmakologie, Medizinischen Fakultät, Rheinisch-Westfälische Technische Hochschule Aachen, F.R.G.

出版信息

Eur J Pharmacol. 1990 Mar 27;178(3):333-42. doi: 10.1016/0014-2999(90)90112-j.

DOI:10.1016/0014-2999(90)90112-j

PMID:2160371

Abstract

The effects of the antidiarrheal drug, loperamide, on HCO3 and Na transport across guinea-pig gallbladder epithelium were investigated using Ussing-chamber methods. Under basal conditions, mucosal loperamide (10(-4) mol/l) moderately lowered both the absorptive (JHCO3ms) and the secretory HCO3 flux (JHCO3sm) (pH-stat method), most likely by changing paracellular HCO3 flow. Exposure to serosal prostaglandin E1 (10(-6) mol/l) abolished Na absorption and turned HCO3 secretion electrogenic. The associated short-circuit current (Isc) was inhibited by loperamide in a concentration-dependent manner; mucosal addition (threshold at 3 x 10(-6) mol/l) of the drug was more effective. Inhibition of Isc was related to a decrease in JHCO3sm, but exceeded the drop in JHCO3net. The effects on JHCO3sm and Isc were mimicked by [Met5]enkephalin. Naloxone (10(-6) mol/l) was unable to influence the effects of loperamide and [Met5]enkephalin on Isc. There were no pro-absorptive effects of loperamide on unidirectional Na fluxes. We conclude that antisecretory properties of loperamide are solely due to inhibition of electrogenic HCO3 secretion, an effect unrelated to opiate receptor binding.

摘要

采用Ussing槽法研究了止泻药洛哌丁胺对豚鼠胆囊上皮细胞HCO₃和Na转运的影响。在基础条件下，黏膜给予洛哌丁胺（10⁻⁴mol/L）可适度降低吸收性HCO₃通量（JHCO₃ms）和分泌性HCO₃通量（JHCO₃sm）（pH稳态法），最可能是通过改变细胞旁HCO₃流来实现的。给予浆膜前列腺素E1（10⁻⁶mol/L）可消除Na吸收并使HCO₃分泌变为电生性。相关的短路电流（Isc）受到洛哌丁胺浓度依赖性抑制；黏膜添加药物（阈值为3×10⁻⁶mol/L）更有效。Isc的抑制与JHCO₃sm的降低有关，但超过了JHCO₃净通量的下降。[Met5]脑啡肽可模拟对JHCO₃sm和Isc的影响。纳洛酮（10⁻⁶mol/L）无法影响洛哌丁胺和[Met5]脑啡肽对Isc的作用。洛哌丁胺对单向Na通量没有促吸收作用。我们得出结论，洛哌丁胺的抗分泌特性完全是由于抑制了电生性HCO₃分泌，这一作用与阿片受体结合无关。