CARRIER-MEDIATED TRANSPORT IS INVOLVED IN MUCOSAL SUCCINATE UPTAKE BY RAT LARGE-INTESTINE

Mucosal uptake of succinate across the luminal epithelial border in various segments of the large intestine of the rat (proximal and distal colon, caecum) was investigated using an in vitro mucosal uptake technique. For comparison, some experiments with jejunal preparations were also performed. Additionally, disappearance of succinate from the lumen of ligated loops of the proximal and distal colon was measured in vivo. In the ligated loop experiments, the succinate concentration of the instilled solution significantly decreased during a period of 30 min in both colonic segments, indicating absorption of succinate. The in vitro experiments revealed a distinct Na+ dependence of mucosal succinate uptake in all intestinal segments investigated. Because succinate uptake by the colonic mucosa of germ-free rats was similarly enhanced in the presence of Na+ compared with Na+-free conditions, measured uptake appears to be due to mucosal uptake rather than to Na+-dependent uptake of succinate by bacteria associated with the mucosa. The evaluation of the kinetics of succinate transport in the proximal colon and jejunum, respectively, revealed a single, Na+-dependent saturable component and a diffusive component in both intestinal segments. With respect to the apparent kinetic parameters of the carrier-mediated transport component, the transport capacity (V(max)) of the jejunal carrier appears to be substantially higher compared with the colonic mechanism (80 and 11 nmol cm-2 (5 min)-1, respectively) whereas the affinity constants (K(m)) did not differ markedly in both segments (0.67 and 0.41 mmol 1-1, respectively). Mucosal uptake of C-14-labelled succinate in the proximal colon was inhibited by unlabelled succinate, fumarate, citrate and tricarballylate, but not by glutamate, L-leucine or butyrate. Na+-dependent uptake of the tricarboxylate tricarballylate but not of the dicarboxylate succinate was significantly enhanced by lowering the pH from 7.0 to 5.5, indicating preferential transport of the protonated forms of tricarboxylates. It is concluded from the present results that a Na+-dependent, saturable carrier is involved in the uptake of structurally related tri- and dicarboxylates by the colonic mucosa of the rat.