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This Article Full Text Full Text (PDF) All Versions of this Article: 288/6/G1217    most recent 00415.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Vidyasagar, S. Articles by Rajendran, V. M. Search for Related Content PubMed PubMed Citation Articles by Vidyasagar, S. Articles by Rajendran, V. M.

MUCOSAL BIOLOGY

Role of short-chain fatty acids in colonic HCO₃ secretion

Departments of ¹Internal Medicine, ²Cellular and Molecular Physiology, and ³Surgery, Yale University, New Haven, Connecticut

Submitted 15 September 2004 ; accepted in final form 14 January 2005

Luminal isobutyrate, a relatively poor metabolized short-chain fatty acid (SCFA), induces HCO₃ secretion via a Cl-independent, DIDS-insensitive, carrier-mediated process as well as inhibiting both Cl-dependent and cAMP-induced HCO₃ secretion. The mechanism(s) responsible for these processes have not been well characterized. HCO₃ 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 HCO₃ secretion is greater than that by isobutyrate, suggesting that both SCFA transport and metabolism are critical for HCO₃ secretion. Both lumen and serosal 25 mM butyrate inhibit cAMP-induced HCO₃ secretion to a comparable degree (98 vs. 90%). In contrast, Cl-dependent HCO₃ secretion is downregulated by lumen 25 mM butyrate considerably more than by serosal butyrate (98 vs. 37%). Butyrate did not induce HCO₃ secretion in isolated microperfused crypts, whereas an outward-directed HCO₃ gradient-driven induced ¹⁴C-butyrate uptake by surface but not crypt cell AMV. Both ³⁶Cl/HCO₃ exchange and potential-dependent ³⁶Cl movement in AMV were inhibited by 96–98% by 20 mM butyrate. We conclude that 1) SCFA-dependent HCO₃ secretion is the result of SCFA transport across the apical membrane via a SCFA/HCO₃ exchange more than intracellular SCFA metabolism; 2) SCFA-dependent HCO₃ secretion is most likely a result of an apical membrane SCFA/HCO₃ exchange in surface epithelial cells; 3) SCFA downregulates Cl-dependent and cAMP-induced HCO₃ secretion secondary to SCFA inhibition of apical membrane Cl/HCO₃ exchange and anion channel activity, respectively.

Cl/HCO₃ exchange; short-chain fatty acid/HCO₃ exchange; anion channel; pH stat; colonic mucosa

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