Role of short-chain fatty acids in colonic HCO3secretion

Abstract

Luminal isobutyrate, a relatively poor metabolized short-chain fatty acid (SCFA), induces HCO3secretion via a Cl-independent, DIDS-insensitive, carrier-mediated process as well as inhibiting both Cl-dependent and cAMP-induced HCO3secretion. The mechanism(s) responsible for these processes have not been well characterized. HCO3secretion 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, and36Cl 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 HCO3secretion is greater than that by isobutyrate, suggesting that both SCFA transport and metabolism are critical for HCO3secretion. Both lumen and serosal 25 mM butyrate inhibit cAMP-induced HCO3secretion to a comparable degree (98 vs. 90%). In contrast, Cl-dependent HCO3secretion is downregulated by lumen 25 mM butyrate considerably more than by serosal butyrate (98 vs. 37%). Butyrate did not induce HCO3secretion in isolated microperfused crypts, whereas an outward-directed HCO3gradient-driven induced14C-butyrate uptake by surface but not crypt cell AMV. Both36Cl/HCO3exchange and potential-dependent36Cl movement in AMV were inhibited by 96–98% by 20 mM butyrate. We conclude that 1) SCFA-dependent HCO3secretion is the result of SCFA transport across the apical membrane via a SCFA/HCO3exchange more than intracellular SCFA metabolism; 2) SCFA-dependent HCO3secretion is most likely a result of an apical membrane SCFA/HCO3exchange in surface epithelial cells; 3) SCFA downregulates Cl-dependent and cAMP-induced HCO3secretion secondary to SCFA inhibition of apical membrane Cl/HCO3exchange and anion channel activity, respectively.