Inhibition of mucosal glycylsarcosine uptake by acetate in rat distal small intestine

Acetate deriving from microbial fermentation may occur at considerable concentrations in the distal small intestine, where it appears to be absorbed by two different mechanisms: acetate-HCO3− exchange and non-ionic diffusion. Whether acetate affects absorption of other nutrients at this intestinal site is not known. Therefore the influence of acetate (30 mmol l−1) on oligopeptide absorption was studied using an in vitro mucosal uptake technique allowing measurement of substrate uptake across the brush border membrane (BBM). Acetate significantly inhibited mucosal uptake of 14C-labelled glycylsarcosine (Gly-Sar) at pH 6 and pH 7 in the presence of sodium. No inhibition occurred in the absence of sodium. Both acetate and the absence of sodium decreased Vmax of mucosal Gly-Sar uptake without substantially affecting the apparent Km value. Since it is well established that Vmax of peptide transport across the intestinal BBM depends on the size of the transmembrane H+ gradient as a driving force the present findings are in accordance with the assumption that acetate inhibits peptide absorption by attenuating the H+ gradient across the BBM, which depends on the presence of sodium.