Mechanisms of acid disposal and acid-stimulated alkaline secretion by gastroduodenal mucosa

This paper investigates acid disposal by gastric and duodenal mucosa with particular reference to the mechanisms of acid-stimulated luminal alkalinization in the duodenum. The bulk of solute flux across duodenal epithelium occurs by paracellular permeation, and passive diffusion of HCO₃via shunt pathways contributes substantially to luminal alkalinization by this tissue in vitro.Effects on epithelial permeability of two treatments which stimulate mucosal alkaline secretion (PGE₂and low luminal pH) were studied in vivoby measuring transmucosal fluxes of radiolabe led urea (mol wt 76) and inulin (mol wt ~ 5000). Rats were anesthetized and rates of alkalinization in segments of distal duodenum perfused with saline were monitored by continuous titration. PGE₂(10 ?M, topically) increased alkaline secretion from 1.63±0.34 to 3.07±0.54?eq/cm/hr (mean ±sem, N=5). Luminal acid exposure (10 mM HCl for 10 min) increased alkalinization rate from 1.54±0.43 to 2.69±0.76; subsequent addition of PGE₂induced a further rise to 3.27±0.54. Recovery of inulin in the luminal perfusate following intravenous injection was <10% of that of urea. Topical PGE₂had little or no effect on recovery of either marker. Luminal acidification increased the rate of appearance of urea by 130±30% (P < 0.01, N=6); recovery of inulin rose slightly but did not achieve statistical significance compared with control. Thus stimulation of mucosal alkaline secretion by luminal PGE₂or acid are associated with differential effects on mucosal permeability. We conclude that low luminal pH enhances permeability of duodenal epithelium and increases the rate of alkalinization as a result of a rise in passive diffusion of HCO₃from the mucosa into the lumen. PGE₂produces no changes in permeability in this model and presumably acts as a result of stimulating transport of HCO₃via a transcellular mechanism as previously demonstrated in vitro.