Immunohistochemic al and functional characterization of pH-dependent intestinal absorption of weak organic acids by the monocarboxylic acid transporter MCT1

The participation of the monocarboxylic acid transporter MCT1 in the intest inal absorption of weak organic acids has been clarified by functional char acterization, by use of stably transfected cells, and by immunohistochemica l location of the transporter in intestinal tissues. Immunohistochemical analysis by use of the anti-MCT1 antibody showed that M CT1 is distributed throughout the upper and lower intestines, especially in the basolateral membrane and, to a lesser extent, in the brush-border memb rane. When the transporter gene rat MCT1 was transfected into MDA-MB231 cel ls, transport of benzoic acid, a model weak organic acid that has been gene rally believed to be transported across the cell membranes by passive diffu sion, and lactic acid in rat MCT1-transfected cells was significantly incre ased compared with transport in cells transfected with the expression vecto r pRc-CMV alone (mock cells). The observed transport was pH-dependent and a ctivity increased between pH 7.5 and pH 5.5, whereas pH-dependence in mock cells was moderate. Rat MCT1-mediated benzoic acid uptake was saturable, wi th an apparent Km value of 3.05 mM. In addition, MCT1 increased the efflux of [C-14]benzoic acid from the cells. Several weak organic acids were also transported by rat MCT1. These results show that pH-dependent intestinal absorption of weak organic acids, previously explained in terms of passive diffusion according to the pH-partition hypothesis, is at least partially accounted for by MCT1-mediat ed transport energized at acidic pH by utilization of the proton gradient a s a driving force.