Three distinct mechanisms of HC[O.sup.-.sub.3] secretion in rat distal colon

HC[O.sup.-.sub.3] secretion has long been recognized in the mammalian colon, but it has not been well characterized. Although most studies of colonic HC[O.sup.-.sub.3] secretion have revealed evidence of lumen [Cl.sup.-] dependence, suggesting a role for apical membrane [Cl.sup.-]/HC[O.sup.-.sub.3] exchange, direct examination of HC[O.sup.-.sub.3] secretion in isolated crypt from rat distal colon did not identify [Cl.sup.-]-dependent HC[O.sup.-.sub.3] secretion but did reveal cAMP-induced, [Cl.sup.-] -independent HC[O.sup.-.sub.3] secretion. Studies were therefore initiated to determine the characteristics of HC[O.sup.-.sub.3] secretion in isolated colonic mucosa to identify HC[O.sup.-.sub.3] secretion in both surface and crypt cells. HC[O.sup.-.sub.3] secretion was measured in rat distal colonic mucosa stripped of muscular and serosal layers by using a pH star technique. Basal HC[O.sup.-.sub.3] secretion (5.6 [+ or -] 0.03 [micro]eq x [h.sup.-1] x [cm.sup.-2]) was abolished by removal of either lumen [Cl.sup.-] or bath HC[O.sup.-.sub.3]; this [Cl.sup.-]-dependent HC[O.sup.-.sub.3] secretion was also inhibited by 100 [micro]M DIDS (0.5 [+ or -] 0.03 [micro]eq x [h.sup.-1] x [cm.sup.-2]) but not by 5-nitro-3-(3-phenylpropyl-amino) benzoic acid (NPPB), a [Cl.sup.-] channel blocker. 8-Bromo-cAMP induced [Cl.sup.-] -independent HC[O.sup.-.sub.3] secretion (and also inhibited [Cl.sup.-] dependent HC[O.sup.-.sub.3] secretion), which was inhibited by NPPB and by glibenclamide, a CFTR blocker, but not by DIDS. Isobutyrate, a poorly metabolized short-chain fatty acid (SCFA), also induced a [Cl.sup.-] -independent. DIDS-insensitive, saturable HC[O.sup.-.sub.3] secretion that was not inhibited by NPPB. Three distinct HC[O.sup.-.sub.3] secretory mechanisms were identified: 1) [Cl.sup.-] -dependent secretion associated with apical membrane [Cl.sup.-]/HC[O.sup.-.sub.3] exchange, 2) cAMP-induced secretion that was a result of an apical membrane anion channel, and 3) SCFA-dependent secretion associated with an apical membrane SCFA/HC[O.sup.-.sub.3] exchange. chloride/bicarbonate exchange; short-chain fatty acid/bicarbonate exchange; anion channel; pH stat