Role of short-chain fatty acids in colonic HCO 3 secretion

Abstract

Luminal isobutyrate, a relatively poor metabolized short-chain fatty acid (SCFA), induces HCO 3 secretion via a Cl-independent, DIDS-insensitive, carrier-mediated process as well as inhibiting both Cl-dependent and cAMP-induced HCO 3 secretion. The mechanism(s) responsible for these processes have not been well characterized. HCO 3 secretion was measured in isolated colonic mucosa mounted in Lucite chambers using pH stat technique and during microperfusion of isolated colonic crypts. 14C-labeled butyrate, 14C-labeled isobutyrate, and 36Cl uptake were also determined by apical membrane vesicles (AMV) isolated from surface and/or crypt cells. Butyrate stimulation of Cl-independent, DIDS-insensitive 5-nitro-3-(3-phenylpropyl-amino)benzoic acid-insensitive HCO 3 secretion .is greater than that by isobutyrate, suggesting that both SCFA transport and metabolism are critical for HCO 3 secretion. Both lumen and serosal 25 mM butyrate inhibit cAMP-induced HCO 3 secretion to a comparable degree (98 vs. 90%). In contrast, Cl-dependent HCO 3 secretion is downregulated by lumen 25 mM butyrate considerably more than by serosal butyrate (98 vs. 37%). Butyrate did not induce HCO 3 secretion in isolated microper-fused crypts, whereas an outward-directed HCO 3 gradient-driven induced 14C- butyrate uptake by surface but not crypt cell AMV. Both 36Cl/HCO 3 exchange and potential-dependent 36Cl movement in AMV were inhibited by 96-98% by 20 mM butyrate. We conclude that 1) SCFA-dependent HCO 3 secretion is the result of SCFA transport across the apical membrane via a SCFA/HCO 3 exchange more than intracellular SCFA metabolism; 2) SCFA-dependent HCO 3 secretion is most likely a result of an apical membrane SCFA/HCO 3 exchange in surface epithelial cells; 3) SCFA downregulates Cl-dependent and cAMP-induced HCO 3 secretion secondary to SCFA inhibition of apical membrane Cl/HCO 3 exchange and anion channel activity, respectively. Copyright © 2005 the American Physiological Society.