Acid-base effects on electrolyte transport in CA II-deficient mouse colon.
To determine the role of carbonic anhydrase (CA) in colonic electrolyte transport, we studied Car-2(0) mice, mutants deficient in cytosolic CA II. Ion fluxes were measured under short-circuit conditions in an Ussing chamber. CA was analyzed by assay and Western blots. In Car-2(0) mouse colonic mucosa, total CA activity was reduced 80% and cytosolic CA I and membrane-bound CA IV activities were not increased. Western blots confirmed the absence of CA II in Car-2(0) mice. Normal mouse distal colon exhibited net Na(+) and Cl(-) absorption, a serosa-positive PD, and was specifically sensitive to pH. Decrease in pH stimulated active Na(+) and Cl(-) absorption whether it was caused by increasing solution PCO(2), reducing HCO(-)(3) concentration, or reducing pH in CO(2)/HCO(-)(3)-free HEPES-Ringer solution. Membrane-permeant methazolamide, but not impermeant benzolamide, at 0.1 mM prevented the effects of pH. Car-2(0) mice exhibited similar basal transport rates and responses to pH and CA inhibitors. We conclude that basal and pH-stimulated colonic electrolyte absorption in mice requires CA I. CA II and IV may have accessory roles.
Goldfarb
D S
DS
Nephrology Section, Veterans Affairs Medical Center and New York University School of Medicine, New York, New York 10010, USA.
Sly
W S
WS
Waheed
A
A
Charney
A N
AN
D000136:Acid-Base Equilibrium / Q000502:physiology*; D000818:Animals; D001574:Benzolamide / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D003106:Colon / Q000201:enzymology; D004573:Electrolytes / Q000378:metabolism*; D005260:Female; D015151:Immunoblotting; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008704:Methazolamide / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains / Q000235:genetics
D002257:Carbonic Anhydrase Inhibitors; D004573:Electrolytes; D007527:Isoenzymes; D002256:Carbonic Anhydrases; D001574:Benzolamide; D008704:Methazolamide