HCO3- secretion in the rat colonic crypt is closely linked to Cl- secretion

Background & Aims: The mechanism of colonic HCO3- secretion has not been es tablished largely because of a lack of experimental methods for its detaile d study, The present studies were designed to establish whether the isolate d, perfused crypt of the rat distal colon is an excellent model to study HC O3- movement and the mechanism of colonic HCO3- secretion, Methods: HCO3- s ecretion was determined in isolated, microperfused crypts by measuring [HCO 3-] by microcalorimetry on nanoliter samples, Results: Net HCO3- absorption was observed during lumen and bath perfusion with an HCO,3--Ringer solutio n, Vasoactive intestinal polypeptide (60 nmol/L), acetylcholine (100 nmol/L ), or dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP, 0.5 mmol/L) i nduced active HCO3- secretion that required bath but not lumen HCO3-/CO2. D BcAMP-stimulated HCO3- secretion was not affected by acetazolamide, an inhi bitor of carbonic anhydrase, Removal of lumen Cl- did not alter DBcAMP-stim ulated HCO3- secretion but reduced fluid secretion. DBcAMP-stimulated HCO3- secretion was closely linked to active Cl- secretion because HCO3- secreti on was substantially reduced by removal of bath Cl-, by addition of bath bu metanide, an inhibitor of Na-K-2Cl cotransport and Cl- secretion, and by ad dition of lumen NPPB, a Cl- channel inhibitor, Conclusions: These studies e stablish that colonic crypt HCO3- secretion (1) is not a result of an apica l membrane Cl--HCO3- exchange, (2) is tightly associated with Cl- secretion , and (3) primarily occurs via an apical membrane Cl- channel.