Acute adaptive cellular base uptake in rat duodenal epithelium

We studied the role of duodenal cellular ion transport in epithelial defens e mechanisms in response to rapid shifts of luminal pH. We used in vivo mic roscopy to measure duodenal epithelial cell intracellular pH (pH(i)), mucus gel thickness, blood flow, and HCO3- secretion in anesthetized rats with o r without the Na+/H+ exchange inhibitor 5-(N,N-dimethyl)-amiloride (DMA) or the anion transport inhibitor DIDS. During acid perfusion pH(i) decreased, whereas mucus gel thickness and blood flow increased, with pH(i) increasin g to over baseline (overshoot) and blood flow and gel thickness returning t o basal levels during subsequent neutral solution perfusion. During a secon d brief acid challenge, pH(i) decrease was lessened (adaptation). These are best explained by augmented cellular HCO3- uptake in response to perfused acid. DIDS, but not DMA, abolished the overshoot and pH(i) adaptation and d ecreased acid-enhanced HCO3- secretion. In perfused duodenum, effluent tota l CO2 output was not increased by acid perfusion, despite a massive increas e of titratable alkalinity, consistent with substantial acid back diffusion and modest CO2 back diffusion during acid perfusions. Rapid shifts of lumi nal pH increased duodenal epithelial buffering power, which protected the c ells from perfused acid, presumably by activation of Na+-HCO3- cotransport. This adaptation may be a novel, important, and early duodenal protective m echanism against rapid physiological shifts of luminal acidity.