Abstract
Epithelial ion transporters and carbonic anhydrase (CA) participate in the regulation of intracellular pH (pHi) in duodenal villous cells. Luminal acid or elevated luminal pCO2 (CO2 stress) acidifies duodenal epithelial cells. The Na/H exchange-1 (NHE-1) inhibitor dimethyl amiloride (DMA) or the Na:HCO3− cotransport (NBC) inhibitor DIDS enhances cellular acidification, whereas the CA inhibitors methazolamide (MTZ) or benzolamide (BNZ) abrogates acidification. We examined the effects of these inhibitors on pHi under CO2 stress in mouse duodenum. Mouse duodenal villous cells were exposed and loaded with a pH-sensitive fluorescence dye BCECF, and pHi was measured with in vivo fluorescent microscope. Duodenal mucosa was exposed to high CO2 solution (pH 6.4, pCO2 260 Torr) with or without DMA (0.1 mM), DIDS (1 mM), MTZ (1 mM), BNZ (1 μM) or novel cell-impermeant CA inhibitor sulfonamide compounds. CO2−stress rapidly acidified the cells followed by pHi recovery to the baseline after CO2 removal. DMA enhanced CO2-induced pHi decrease, whereas DIDS and MTZ reduced the acidification. BNZ and the cell-impermeant CA inhibitors had no effect. The divergent effects of DMA and DIDS on pHi suggest that NHE-1 is more important than is NBC for pHi regulation. Compared with complete inhibition of CO2−induced acidification by MTZ or BNZ in rat duodenum, MTZ was less effective, and the impermeant CA inhibitors had no effect in mouse duodenum, consistent with a marked species difference between rat and mouse for pHi regulation by CA and by plasma membrane acid-base transporters.
Published Version
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