Open AccessDamage to the gastric epithelium activates cellular bicarbonate secretion via SLC26A9 Cl−/HCO3−exchange
Author(s) -
Elise S. Demitrack,
Manoocher Soleimani,
Marshall H. Montrose
Publication year - 2010
Publication title -
american journal of physiology. gastrointestinal and liver physiology/american journal of physiology: gastrointestinal and liver physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.644
H-Index - 169
eISSN - 1522-1547
pISSN - 0193-1857
DOI - 10.1152/ajpgi.00037.2010
Subject(s) - bicarbonate , chemistry , ion exchange , secretion , charge exchange , epithelium , radiochemistry , physics , biochemistry , ion , medicine , pathology , organic chemistry
Gastric surface pH (pH(o)) transiently increases in response to focal epithelial damage. The sources of that increase, either from paracellular leakage of interstitial fluid or transcellular acid/base fluxes, have not been determined. Using in vivo microscopy approaches we measured pH(o) with Cl-NERF, tissue permeability with intravenous fluorescent-dextrans to label interstitial fluid (paracellular leakage), and gastric epithelial intracellular pH (pH(i)) with SNARF-5F (cellular acid/base fluxes). In response to two-photon photodamage, we found that cell-impermeant dyes entered damaged cells from luminal or tissue compartments, suggesting a possible slow transcellular, but not paracellular, route for increased permeability after damage. Regarding cytosolic acid/base status, we found that damaged cells acidified (6.63 +/- 0.03) after photodamage, compared with healthy surface cells both near (7.12 +/- 0.06) and far (7.07 +/- 0.04) from damage (P < 0.05). This damaged cell acidification was further attenuated with 20 muM intravenous EIPA (6.34 +/- 0.05, P < 0.05) but unchanged by addition of 0.5 mM luminal H(2)DIDS (6.64 +/- 0.08, P > 0.05). Raising luminal pH did not realkalinize damaged cells, suggesting that the mechanism of acidification is not attributable to leakiness to luminal protons. Inhibition of apical HCO(3)(-) secretion with 0.5 mM luminal H(2)DIDS or genetic deletion of the solute-like carrier 26A9 (SLC26A9) Cl(-)/HCO(3)(-) exchanger blocked the pH(o) increase normally observed in control animals but did not compromise repair of damaged tissue. Addition of exogenous PGE(2) significantly increased pH(o) in wild-type, but not SLC26A9 knockout, animals, suggesting that prostaglandin-stimulated HCO(3)(-) secretion is fully mediated by SLC26A9. We conclude that cellular HCO(3)(-) secretion, likely through SLC26A9, is the dominant mechanism whereby surface pH transiently increases in response to photodamage.