Non-catalytic role of carbonic anhydrase in rat intestinal absorption

Abstract

Carbonic anhydrase (CA) inhibition reduces NaCl absorption in rat distal ileum, a pH-sensitive, low CA activity tissue, and in distal colon, a CO 2-sensitive, high CA activity tissue. We hypothesized that CA plays a non-catalytic role in NaCl absorption in these segments. Unidirectional fluxes of Na + and Cl −, and total HCO 3 − generation (estimated as the sum of radiolabeled HCO 3 − and CO 2 produced from glucose) were measured in Ussing chambers in nominally CO 2, HCO 3 −-free HEPES Ringer. Measurements were made in the presence and absence of 0.1 mM methazolamide, a membrane-permeant CA inhibitor. Ringer pH reduction from 7.6 to 7.1 stimulated ileal but not colonic Na + and Cl − absorption. In the ileum, methazolamide reduced J ms Na and J ms Cl and caused net Cl − secretion at pH 7.6, and prevented the stimulatory effect of lowering pH. In the colon, methazolamide reduced Na + and Cl − absorption at pH 7.6. Total HCO 3 − generation was minimal in HEPES at pH 7.6 and 7.1 in both segments, was minimally affected by methazolamide, and did not account for the changes in Cl − absorption caused by pH or methazolamide. We conclude that CA plays a role in ileal and colonic NaCl absorption independent of its catalytic function.