Asymmetric anion exchange
Butyrate-gradient-stimulated Cl uptake
Springer Online Journal Archives 1860-2000
Chemistry and Pharmacology
Abstract The cellular model of short chain fatty acid stimulation of electroneutral Na-Cl absorption in large intestine proposes that SCFA, following its uptake across the apical membrane, recycles and is coupled to functional Na-H and Cl-short chain fatty acid exchanges. To establish the presence of a Cl-butyrate exchange (used as a model short chain fatty acid), studies of 36Cl and 14C-butyrate uptake across apical membrane vesicles of rat distal colon were performed. An outward butyrate-gradient stimulated transient accumulation of 36Cl uptake that was not inhibited by pH clamping with valinomycin (a K ionophore) and FCCP (a proton ionophore). Outward butyrate-gradient-stimulated 36Cl uptake was inhibited by 4,4′-diisothiocyanatostilbene2,2′-disulfonic acid (DIDS) with a half-maximal inhibitory concentration (IC50) of 68.4 μm, and was saturated by both increasing extravesicular Cl concentration (K m for Cl of 26.8 ±3.4 mm and a V max of 12.4±0.6 nmol/mg protein·9 sec) and increasing intravesicular butyrate concentration (K m for butyrate of 5.9 mm and a V max for Cl of 5.9 nmol/mg protein · 9 sec). 36Cl uptake was also stimulated by outward gradients of other short chain fatty acids (e.g., propionate, acetate and formate). In contrast, an outward Cl gradient failed to enhance 14C-butyrate uptake. Extravesicular Cl more than extravesicular butyrate enhanced 36Cl efflux from apical membrane vesicles. These studies provide compelling evidence for the presence of an electroneutral, pH-activated, Cl-butyrate exchange which in concert with Na-H exchange is the mechanism by which butyrate stimulates electroneutral Na-Cl absorption.
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