Nonionic diffusion of short-chain fatty acids across rat colon

Short-chain fatty acid (SCFA) transport across the colon may occur by nonionic diffusion and/or via apical membrane SCFA⁻/${HCO}_3^{-}$ exchange. To examine the relative importance of these processes, stripped segments of rat (Ratus ratus) proximal and distal colon were studied in Ussing chambers, and the unidirectional fluxes of radiolabeled SCFA butyrate, propionate, or weakly metabolized isobutyrate were measured. InN-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid (HEPES) or 1 or 5 mM ${HCO}_3^{-}$ Ringer, decreases in mucosal pH stimulated mucosal-to-serosal flux (J_m→s) of all SCFA, decreases in serosal pH stimulated serosal-to-mucosal flux (J_s→m), and bilateral pH decreases stimulated both fluxes equally. These effects were observed whether the SCFA was present on one or both sides of the tissue, in both proximal and distal colon, in the absence of luminal Na⁺, and in the presence of either luminal or serosal ouabain. Changes in intracellular pH or intracellular [${HCO}_3^{-}$ ] did not account for the effects of extracellular pH. Luminal Cl⁻ removal, to evaluate the role of apical membrane Cl⁻/SCFA⁻exchange, had no effect onJ_m→s but decreasedJ_s→m 32% at pH 6.5 and 22% at 7.2. Increasing SCFA concentration from 1 to 100 mM, at pH 6.4 or 7.4, caused a linear increase inJ_m→s. We conclude that SCFA are mainly transported across the rat colon by nonionic diffusion.