Carrier‐mediated transport is involved in mucosal succinate uptake by rat large intestine

Abstract

SUMMARYMucosal 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 (Vmax) of the jejunal carrier appears to be substantially higher compared with the colonic mechanism (80 and 11 nmol cm-2 (5 min)-', respectively) whereas the affinity constants (K.) did not differ markedly in both segments (0 67 and 0 41 mmol 1-1, respectively). Mucosal uptake of 14C-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.

SLC26A6 and NaDC-1 Transporters Interact to Regulate Oxalate and Citrate Homeostasis

“…However, because slc26a6 is expressed in the luminal membrane, the increase most likely reflects increased activity of NaDC-1. Since slc26a6 and NaDC-1 are expressed at a high level in the jejunum, 16,21,22 and slc26a6-mediated jejunal oxalate excretion has a major role in controlling systemic oxalate metabolism, 4 we also used jejuna sheets from slc26a6 2/2 and WT mice and measured the Na + -dependent succinate uptake. Supplemental Figure 1, A and B, shows that deletion of slc26a6 had no effect on the Na + -independent succinate uptake while increasing the Na + -dependent uptake by about 35%.…”

High-protein diet modifies colonic microbiota and luminal environment but not colonocyte metabolism in the rat model: the increased luminal bulk connection

“…Among the 10 monocarboxylic acids that were markedly increased in colonic content, some of them (butyrate, acetate, propionate, and L-lactate) have been shown to represent important luminal oxidative substrates providing energy in the form of ATP for the colonic epithelial cells. In the case of succinate, this metabolite has been shown to be transported within the colonic mucosa (74) and to increase oxygen consumption in colonocytes (31). Because the large intestine epithelial layer is renewed within a few days (with important corresponding anabolic ATP-consuming pathways) (54), together with consumption of ATP by colonocytes through the membrane-bound ATPase involved in colonic electrolyte transport (7), ATP has to be synthesized at a rate matching its cellular utilization to maintain a constant ATP cell content, a necessary condition to maintain the viability of epithelial cells (41).…”

Transport Functions of Riboflavin Carriers in the Rat Small Intestine and Colon: Site Difference and Effects of Tricyclic-Type Drugs

“…To date, the carrier-mediated transport of organic nutrients and drugs in the colon has not been subject to extensive investigation, with the exceptions of monocarboxylates (Ritzhaupt et al 1998a(Ritzhaupt et al , 1998b, dicarboxylates (Wolffram et al 1994), folate Kumar et al 1997), and biotin (Said et al 1998). The small intestine, with a large surface area and abundant carriers, when available is no doubt the major site for the absorption of nutrients and drugs following oral administration.…”