Premium
Epithelial carbonic anhydrases facilitate CO 2 diffusion in rat duodenum
Author(s) -
Mizumori Misa,
Akiba Yasutada,
Takeuchi Tetsu,
Supuran Claudiu T,
Kaunitz Jonathan D
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1227
Subject(s) - chemistry , bicarbonate , carbonic acid , secretion , cytosol , neutralization , duodenum , carbonic anhydrase , acidosis , pco2 , biochemistry , biophysics , medicine , endocrinology , enzyme , biology , organic chemistry , antibody , immunology
Duodenum is the site of mixing gastric H + with secreted HCO 3 − , generating high pCO 2 . We examined the role of membrane‐bound and cytosolic carbonic anhydrases (CA) in H + neutralization, CO 2 absorption and HCO 3 − secretion. Rat duodena were perfused with different pH and pCO 2 solutions with or without permeant CA inhibitor (CAI) methazolamide (MTZ) or novel impermeant CAIs. Flow‐through pH and CO 2 electrodes simultaneously measured perfusate and effluent pH and pCO 2 . Luminal high CO 2 (pH 6.4, 260 Torr) increased net CO 2 loss from the perfusate, accompanied by increased portal venous (PV) [H + ] and pCO 2 . Impermeant CAIs abolished the net CO 2 loss and increased HCO 3 − secretion, whereas all CAIs inhibited PV [H + ] and pCO 2 increase. Luminal acid decreased CO 2 secretion and increased H + loss with PV [H + ] and pCO 2 increase, all inhibited by MTZ. Luminal acidity enhanced CO 2 loss, but high luminal CO 2 decreased H + loss. Net CO 2 loss during 30% CO 2 buffer (pH 6.5) perfusion was inhibited by MTZ and delayed by impermeant CAIs. Perfused 13 CO 2 was significantly increased in PV 10 min after the challenge, inhibited by all CAIs. H + and CO 2 loss from the perfusate were accompanied by increases of PV H + and tracer CO 2 , but unchanged PV total CO 2 , consistent with transmucosal net H + and tracer CO 2 movement, which was inhibited by MTZ or impermeant CAIs. Inhibition of membrane‐bound CAs augments HCO 3 − secretion, normally obscured by high luminal [CO 2 ]. The duodenum absorbs luminal acid by neutralization with secreted HCO 3 − to CO 2 , absorption of CO 2 , cytosolic conversion of CO 2 to H + and transport of cellular H + to subepithelium and to PV. Membrane‐bound and cytosolic CAs cooperatively facilitate HCO 3 − secretion into lumen and CO 2 diffusion into duodenal mucosa, serving as important acid‐base regulators.