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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Abbreviations
- AMV:
-
apical membrane vesicles
- BLMV:
-
basolateral membrane vesicles
- DIDS:
-
4,4′-diisothiocyanatostilbene 2,2′-disulfonic acid
- FCCP:
-
carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone
- MES:
-
1-[N-morpholino]ethanesulfonic acid
- NMG:
-
N-memyl-d-glucamine
- SCF:
-
Ashort chain fatty acid
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This study was supported in part by a Public Health Service research Grant (DK 14669) provided by the National Institute of Diabetes, Digestive and Kidney Diseases. Ms. Mary Guidone provided excellent secretarial assistance.
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Rajendran, V.M., Binder, H.J. Apical membrane Cl-butyrate exchange: Mechanism of short chain fatty acid stimulation of active chloride absorption in rat distal colon. J. Membarin Biol. 141, 51–58 (1994). https://doi.org/10.1007/BF00232873
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DOI: https://doi.org/10.1007/BF00232873