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Title: Bile acid inhibition of taurocholate uptake by rat hepatocytes: role of OH groups

Abstract

To define further the structural specificity of the taurocholate uptake site, the authors studied the ability of a variety of taurine-conjugated bile acids with differing hydroxyl substituents on the sterol moiety to inhibit (/sup 14/C) taurocholate uptake. Rat hepatocytes isolated by collagenase perfusion were incubated in a tris (hydroxymethyl) aminomethane-phosphate buffer containing (/sup 14/C)taurocholate in the presence or absence of inhibitor bile acid. Stronger inhibitors were studied at a fixed concentration of 5 ..mu..M, weaker ones at 25 ..mu..M. Initial uptake velocity was measured. Uptake velocity could then be related to taurocholate concentration and a V/sub max/ and K/sub m/ could be determined by applying a nonlinear least squares fit to the data obtained with or without inhibitor. The kinetic parameters allowed the determination of the type of inhibition and of inhibition constants (K/sub i/) of the various test bile acids. The data indicate that bile acids containing a 6- or 7-OH group exhibit competitive inhibition, whereas bile acids with no 6- or 7-OH group exhibit noncompetitive inhibition. Of the compounds exhibiting competitive inhibition, K/sub i/ varied with the number of hydroxyl groups on the sterol moiety. They conclude that the presence of absence of a 6- or 7-OH groupmore » dictates the mechanism of inhibition; the number of hydroxyl substituents determines the potency of competitive inhibition.« less

Authors:
; ; ; ;
Publication Date:
Research Org.:
Univ. of Modena, Italy
OSTI Identifier:
5445346
Resource Type:
Journal Article
Resource Relation:
Journal Name: Am. J. Physiol.; (United States); Journal Volume: 252:3
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; BILE ACIDS; BIOCHEMISTRY; CARBON 14 COMPOUNDS; UPTAKE; CHOLIC ACID; BIOCHEMICAL REACTION KINETICS; HYDROXIDES; INHIBITION; INSULIN; LIVER CELLS; RATS; TAURINE; TRITIUM COMPOUNDS; AMINES; ANIMAL CELLS; ANIMALS; CARBOXYLIC ACIDS; CHEMISTRY; HORMONES; HYDROGEN COMPOUNDS; HYDROXY COMPOUNDS; KINETICS; LABELLED COMPOUNDS; MAMMALS; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC SULFUR COMPOUNDS; OXYGEN COMPOUNDS; PEPTIDE HORMONES; REACTION KINETICS; RODENTS; SOMATIC CELLS; STEROIDS; STEROLS; SULFONIC ACIDS; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Bellentani, S., Hardison, W.G.M., Marchegiano, P., Zanasi, G., and Manenti, F.. Bile acid inhibition of taurocholate uptake by rat hepatocytes: role of OH groups. United States: N. p., 1987. Web.
Bellentani, S., Hardison, W.G.M., Marchegiano, P., Zanasi, G., & Manenti, F.. Bile acid inhibition of taurocholate uptake by rat hepatocytes: role of OH groups. United States.
Bellentani, S., Hardison, W.G.M., Marchegiano, P., Zanasi, G., and Manenti, F.. Sun . "Bile acid inhibition of taurocholate uptake by rat hepatocytes: role of OH groups". United States. doi:.
@article{osti_5445346,
title = {Bile acid inhibition of taurocholate uptake by rat hepatocytes: role of OH groups},
author = {Bellentani, S. and Hardison, W.G.M. and Marchegiano, P. and Zanasi, G. and Manenti, F.},
abstractNote = {To define further the structural specificity of the taurocholate uptake site, the authors studied the ability of a variety of taurine-conjugated bile acids with differing hydroxyl substituents on the sterol moiety to inhibit (/sup 14/C) taurocholate uptake. Rat hepatocytes isolated by collagenase perfusion were incubated in a tris (hydroxymethyl) aminomethane-phosphate buffer containing (/sup 14/C)taurocholate in the presence or absence of inhibitor bile acid. Stronger inhibitors were studied at a fixed concentration of 5 ..mu..M, weaker ones at 25 ..mu..M. Initial uptake velocity was measured. Uptake velocity could then be related to taurocholate concentration and a V/sub max/ and K/sub m/ could be determined by applying a nonlinear least squares fit to the data obtained with or without inhibitor. The kinetic parameters allowed the determination of the type of inhibition and of inhibition constants (K/sub i/) of the various test bile acids. The data indicate that bile acids containing a 6- or 7-OH group exhibit competitive inhibition, whereas bile acids with no 6- or 7-OH group exhibit noncompetitive inhibition. Of the compounds exhibiting competitive inhibition, K/sub i/ varied with the number of hydroxyl groups on the sterol moiety. They conclude that the presence of absence of a 6- or 7-OH group dictates the mechanism of inhibition; the number of hydroxyl substituents determines the potency of competitive inhibition.},
doi = {},
journal = {Am. J. Physiol.; (United States)},
number = ,
volume = 252:3,
place = {United States},
year = {Sun Mar 01 00:00:00 EST 1987},
month = {Sun Mar 01 00:00:00 EST 1987}
}