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Am J Physiol Gastrointest Liver Physiol 280: G1083-G1092, 2001;
0193-1857/01 $5.00
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Vol. 280, Issue 6, G1083-G1092, June 2001

Acute adaptive cellular base uptake in rat duodenal epithelium

Yasutada Akiba2,5, Osamu Furukawa2,5, Paul H. Guth1, Eli Engel2,3, Igor Nastaskin4, and Jonathan D. Kaunitz1,2,5

1 Greater Los Angeles Veterans Affairs Healthcare System, 2 School of Medicine, and 3 Department of Biomathematics and 4 College of Letters and Science, University of California Los Angeles 90024; and 5 CURE: Digestive Diseases Research Center, Los Angeles, California 90073

We studied the role of duodenal cellular ion transport in epithelial defense mechanisms in response to rapid shifts of luminal pH. We used in vivo microscopy to measure duodenal epithelial cell intracellular pH (pHi), mucus gel thickness, blood flow, and HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> secretion in anesthetized rats with or without the Na+/H+ exchange inhibitor 5-(N,N-dimethyl)-amiloride (DMA) or the anion transport inhibitor DIDS. During acid perfusion pHi decreased, whereas mucus gel thickness and blood flow increased, with pHi increasing to over baseline (overshoot) and blood flow and gel thickness returning to basal levels during subsequent neutral solution perfusion. During a second brief acid challenge, pHi decrease was lessened (adaptation). These are best explained by augmented cellular HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> uptake in response to perfused acid. DIDS, but not DMA, abolished the overshoot and pHi adaptation and decreased acid-enhanced HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> secretion. In perfused duodenum, effluent total CO2 output was not increased by acid perfusion, despite a massive increase of titratable alkalinity, consistent with substantial acid back diffusion and modest CO2 back diffusion during acid perfusions. Rapid shifts of luminal pH increased duodenal epithelial buffering power, which protected the cells from perfused acid, presumably by activation of Na+-HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> cotransport. This adaptation may be a novel, important, and early duodenal protective mechanism against rapid physiological shifts of luminal acidity.

intracellular pH; bicarbonate secretion; mucosal defense; mucus secretion; mucosal blood flow


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