Non-catalytic role of carbonic anhydrase in rat intestinal absorption.
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.
Charney
Alan N
AN
Nephrology Section, VA Medical Center, New York University School of Medicine, 423 East 23rd Street, New York, NY 10010, USA. alan.charney@med.va.gov
Alexander-Chacko
Jesline
J
Gummaconda
Ramanashree
R
Egnor
Richard W
RW
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001692:Biological Transport; D002245:Carbon Dioxide / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000378:metabolism*; D003106:Colon / Q000378:metabolism*; D006531:HEPES; D006863:Hydrogen-Ion Concentration; D007082:Ileum / Q000378:metabolism*; D007408:Intestinal Absorption; D008297:Male; D008704:Methazolamide / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000378:metabolism
D001639:Bicarbonates; D002257:Carbonic Anhydrase Inhibitors; D002245:Carbon Dioxide; D012965:Sodium Chloride; D002256:Carbonic Anhydrases; D006531:HEPES; D008704:Methazolamide