Substrate and inhibitor specificity of butyrate uptake in apical membrane vesicles of the rat distal colon

Background/Aims: There is substantial evidence that transcellular flux of s hort-chain fatty acid (SCFA) absorption, at least in part, is mediated by a n anion exchange process with bicarbonate. Methods: This anion ex change sy stem was further characterized in apical membrane vesicles of the rat dista l colon by studying substrate and inhibitor specificities of a variety of s ubstituted monocarboxylic acids as well as of known inhibitors of the recen tly described monocarboxylate transporter MCT1 and MCT2, Results: SCFA tran sport was significantly reduced in the presence of branched and unbranched SCFAs and several bromo, chloro and mercapto analogues as well as nicotinic acid and L-lactate, In contrast, known inhibitors of monocarboxylate trans porter proteins like stilbene derivatives, phloretin and 2-cyano-4-hydroxyc innamate did not inhibit bicarbonate-gradient stimulated butyrate transport . Kinetic analysis of increasing substrate concentrations of 3-mercaptoprop ionate, L-lactate and nicotinic acid showed saturation kinetics with appare nt K-i of 6.1, 18.3 and 14.7 mmol/l, respectively. Conclusions: The data no t only confirm earlier results that absorption of SCFAs in apical membranes of the rat distal colon is mediated by a relatively low affinity/high capa city SCFA(-)/HCO3- exchange mechanism, but also indicate that although this anion transporter shares some functional similarities, is not identical wi th the recently cloned MCT isoforms, Copyright (C) 2000 S. Karger AG. Basel .