MODULATION OF SECRETAGOGUE-INDUCED CHLORIDE SECRETION BY INTRACELLULAR BICARBONATE

We have previously demonstrated inhibition of basal Cl- secretion by intracellular bicarbonate concentration ([HCO3-](i)) in rat distal colon. We now examined whether secretagogue-induced Cl- secretion is inhibited by [HCO3-](i) as well. Stripped segments of distal colon from male Sprague-Dawley rats and the colon tumor cell line T84 were studied. Flux measurements were performed in the Ussing chamber under short-circuit conditions. [HCO3-](i) was calculated from intracellular pH (pH(i)) values that were estimated with the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) and carbachol were used as secretagogues. In both distal colon and T84 cells, [HCO3-](i) did not affect cAMP-induced Cl- secretion. However, carbachol-induced secretion was inhibited by [HCO3-](i); in rat colon, Cl- secretion decreased from 2.3 to 1.5 mu eq.cm(-2).h(-1) when [HCO3-](i) was increased from 15.0 to 28.4 mM (P < 0.05). In T84 cells, the change in short-circuit current decreased from 8.1 to 1.1 mu A/cm(2) over a range of [HCO3-](i) from 0 to 15.6 mM (P < 0.001). We conclude that [HCO3-](i) is an important modulator of carbachol-stimulated Cl- secretion in both rat distal colon and the T84 cell line. cAMP-mediated secretion is not affected by [HCO3-](i).