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

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...

Full description

Saved in:
Bibliographic Details
Published inEuropean journal of pharmacology Vol. 178; no. 3; p. 333
Main Authors Wehner, F, Winterhager, J M, Petersen, K U
Format Journal Article
LanguageEnglish
Published Netherlands 27.03.1990
Subjects
Alprostadil - pharmacology
Animals
Bicarbonates - metabolism
Biological Transport - drug effects
Electrophysiology
Enkephalin, Methionine - metabolism
Epithelium - drug effects
Epithelium - metabolism
Gallbladder - drug effects
Gallbladder - metabolism
Guinea Pigs
In Vitro Techniques
Intestinal Absorption - drug effects
Loperamide - pharmacology
Male
Naloxone - pharmacology
Piperidines - pharmacology
Receptors, Opioid - drug effects
Sodium - metabolism
Sodium Radioisotopes
Online AccessGet more information

Cover

More Information
Summary: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.
ISSN:0014-2999
1879-0712
DOI:10.1016/0014-2999(90)90112-J