Revised Manuscript Received January 6, 1993 abstract: Gastric parietal cell apical membranes must protect the cell from the extremely low pH and wide variations in osmolality of the gastric juice. To characterize the permeability properties of gastric apical membranes, we have measured passive permeabilities to water, protons, NH3, and small nonelectrolytes of membrane vesicles derived from parietal cells of fasted animals and fed animals. Both preparations are known to be highly enriched in H+/K+-ATPase, the enzyme responsible for acidifying the gastric contents. The preparations behaved as single populations, and their permeability properties were similar in all respects, permitting pooling of the results. This similarity suggests that insertion of tubulovesicles into the apical membrane does not change the behavior of the lipid bilayer. Osmotic water permeability (Pf) averaged (mean±SD)(2.8±0.3) X 10-4 cm/s, a value 10-fold lower than that obtained in lecithin large unilamellar vesicles (LUV) and similar to that obtained in other water-tight epithelia. Similarly, ammonia permeability (Pnh3) was low [(4.4±2.3) X 10~ 3 cm/s] and 10 times below that of lecithin LUV. By contrast, proton permeability (PH+) was surprisingly high (0.030±0.011 cm/s) and similar to that of lecithin LUV. These results suggest that the pathwayfor proton permeation differs from that of water and NH3. Nonelectrolyte permeabilities were strikingly similar to those obtainedin another water-tight epithelium, the toad urinary bladder. Moreover, these permeabilities followed Overton’s rule in that permeability varied in accordance with the oil-water partition coefficient. We conclude that the gastric apical membrane, like that of several renal epithelia, is relatively water-tight and exhibits low permeabilities to small nonelectrolytes. These properties are likely to be essential to the ability of this membrane to perform its barrier function.

The gastric juice has a low pH and a widely varying osmolality, yet the epithelial cells lining the stomach must maintain a relatively constant intracellular osmolality and pH. The stomach’s ability to maintain a proton concentration gradient of greater than 1 000 000-fold has been termed the gastric mucosal barrier (Hirst, 1990). The physiological gastric mucosal barrier includes several anatomical barriers such as the mucus-bicarbonate layer, the apical epithelial membrane lipid bilayer and tight junctions, intracellular buffering and pH regulation, and mucosal blood flow (Wilkes et al., 1989; Allen et al., 1984; Hirst, 1990). Controversy surrounds the role mucus plays; however, it is unlikely to provide a significant barrier to the diffusion of H+ since the mucus layer layer exhibits a limited buffer capacity (Hirst, 1990). Also, since H+ is secreted from the parietal cell beneath the mucosal layer, protons must pass from the parietal cell surface through the mucus to reach the lumen of the stomach. Evidence for the significance of the apical cell membranein the gastric permeability barrier comes from studies with