“First-Pass” Protection Against Luminal Acid in Necturus Antral Epithelium

Abstract

The mechanisms contributing to the “first-pass” protection against intracellular acidosis in acid exposed gastric mucosa are reviewed. The studies were performed with isolated Necturus antral mucosa using microelectrode technique. The following observations are discussed: I.The pre- epithelial mucus-HCO3 buffer layer has a buffer capacity strong enough to maintain a pH gradient between the luminal bulk solution and the epithelial surface in acid-exposed gastric mucosa. Perturbation of this layer by HCO3 inhibition or mucolytic agents leads to dissipation of the pH gradient, with subsequent acidification of intracellular pH. 2. Luminal acid (pH 3.0 – 2.0) increases the apical cell membrane resistance of surface cells by ca 100%, thus decreasing its permeability to luminal H+ (and other ions). 3. In resting antral mucosa, with weak pre-epithelial buffer capacity and permeable apical cell membranes, acute exposure to luminal acid leads to transient acidification of surface cells, which is controlled by activation of basolateral Na+/H+ antiport. After more prolonged acid exposure, the enhanced pre-epithelial buffer capacity (due to stimulated epithelial HC03 secretion) and the tightened apical cell membranes form a diffusion barrier efficient enough to prevent the access of luminal H+ inside surface cells, and the action of Na+/H+ antiport is not needed. However, if these diffusion barriers are deranged, the basolateral Na+/H+ antiport is again activated and becomes the critical regulator of pHj to maintain it within physiological ranges.