Transport of n-butyrate into human colonic luminal membrane vesicles

Human colonic short-chain fatty acid (SCFA) absorption is associated with increased luminal pH and HCO3- and enhanced Na+ absorption. Therefore, the mechanism of colonic SCFA transport, its dependence on Na+ and HCO3- and interactions with Cl-/HCO3-, and Na+/H+ exchangers were characterized. Luminal membrane vesicles (LMV) isolated by divalent cation precipitation from organ donor colons were used for n-butyrate transport. Uptake of n-butyrate into the human colonic LMV was minimal even in the presence of an inward pH gradient, but an outward HCO3- gradient significantly increased uptake rates. HCO3- stimulated butyrate uptake was saturable with an apparent Michaelis constant of 1.5 +/- 0.2 mM and maximal velocity of 105 +/- 3 nmol . mg protein(-1) . 3 s(-1). Intravesicular butyrate resulted in trans-stimulation of n-[1-C-14]butyrate uptake. Butyrate uptake was inhibited similar to 25-40% by C2-C5 SCFAs and similar to 40% by niflumic acid. Butyrate uptake was not affected by extravesicular Na+, and Na-22 uptake was unaltered by extravesicular butyrate. Butyrate uptake was independent of extra- or intravesicular Cl-, and butyrate loading produced no changes in Cl-36 uptake. We conclude that the predominant mechanism of n-butyrate transport across the human colonic luminal membrane appears to be via a HCO3-/SCFA antiport system independent of Cl-/HCO3- exchange and Na+ transport.