INTESTINAL BRUSH-BORDER MEMBRANE-TRANSPORT OF MONOCARBOXYLIC ACIDS MEDIATED BY PROTON-COUPLED TRANSPORT AND ANION ANTIPORT MECHANISMS

Intestinal brush-border membrane transport of monocarboxylic acids was investigated by using rabbit intestinal brush-border membrane vesicle s (BBMVs) and isolated intestinal tissues mounted on Ussing-type chamb ers. [H-3]Mevalonic acid uptake by BBMVs showed an overshoot phenomeno n in the presence of an inwardly directed proton gradient, but not in the presence of an inwardly directed sodium gradient or an outwardly d irected HCO3- or chloride gradient. Initial uptake of mevalonic acid w as saturable in the presence of a proton gradient. Uptake of [H-3]meva lonic acid was inhibited by various monocarboxylic acids, including ac etic acid, benzoic acid, lactic acid, nicotinic acid, pravastatin, sal icylic acid and valproic acid, but not by dicarboxylic acid or amino a cids. Acetic acid, which is transported by both anion antiport and pro ton-coupled transport systems, induced serosal bicarbonate-dependent a lkalinization in the mucosal-side bathing solution of rabbit jejunal t issues, when examined in Ussing-type chambers. Pravastatin, which is a structural analogue of mevalonic acid and is absorbed via proton-coup led transport like mevalonic acid, did not. The result demonstrates th at acetic acid is transported by the bicarbonate-dependent anion antip ort system, whereas pravastatin is not. So, it is suggested that monoc arboxylic acids are transported by at least two independent transporte rs, namely, a proton-coupled transporter for most monocarboxylic acids , including mevalonic acid, pravastatin and acetic acid, and an anion antiporter for acetic acid, but not for mevalonic acid or pravastatin. Activation of anion antiporter can induce HCO3- secretion in intact i ntestine.