MODULATION OF CHLORIDE SECRETION IN THE RAT ILEUM BY INTRACELLULAR BICARBONATE

Increasing intracellular bicarbonate concentration ([HCO3-](i)) inhibi ts calcium-mediated Cl- secretion in rat distal colon and T84 cells. W e investigated the effect of [HCO3-](i) on Cl- secretion in rat ileum. Segments of intact ileum from Sprague-Dawley rats were studied in Uss ing chambers and villus and crypt intracellular pH and [HCO3-](i) were determined using BCECF. A range of crypt and villus [HCO3-](i) from 0 to 31 mM was obtained by varying Ringer's composition. Basal serosal- to-mucosal Cl- flux (J(sm)(Cl)) averaged 8.5 +/- 0.2 mu eq . h(-1) . c m(-2) and was unaffected by changing [HCO3-](i) or serosal bumetanide. Carbachol increased J(sm)(Cl) by 3.9 +/- 0.5 mu eq . h(-1) . cm(-2) a t [HCO3-](i) = 0 mM but only by 1.0 +/- mu eq . h(-1) . cm(-2) at high crypt and villus [HCO3-](i). Dibutyryl-cAMP increased J(sm)(Cl) by 2. 5 +/- 0.2 mu eq . h(-1) . cm(-2) at all [HCO3-](i). Carbachol and db-c AMP showed mutual antagonism at low [HCO3-](i) and near-additivity at high [HCO3-](i). We conclude that like rat colon and T84 cells, calciu m-mediated but not cAMP-mediated Cl- secretion in the ileum is inhibit ed by increasing [HCO3-](i). Mutual antagonism between carbachol and d b-cAMP at low [HCO3-](i) was present in ileum and distal colon but not in T84 cells. (C) 1997 Elsevier Science Inc.