The role of cyclooxygenase activity in regulation of gastric surfacepH.

摘要

The epithelial cells that form the luminal surface of the stomach are continually exposed to an acidic environment. It is thought that these surface cells are protected by an alkaline layer that forms between the interface of luminal contents and the surface epithelia. The goal of these studies was to determine mechanisms regulating the protective alkaline layer. A method of in vivo confocal microscopy in mice was developed for examining events at the gastric surface. Results from these studies showed that net alkali secretion was seen in response to the fasted luminal pH (pH3), forming a pH gradient most alkaline directly at the gastric surface and becoming more acidic at distances further away from the tissue. In response to fed luminal pH (pH5), a net acid secretion was seen by the stomach, forming a pH gradient most acidic at the gastric surface and becoming more alkaline at distances further from the tissue. Although the pH gradient qualitatively switches in orientation, the pH directly at the gastric surface was sustained near pH 4. When the amount of acid presented to the gastric surface per minute was increased, the pH at the gastric surface remained near pH 4 even though the thickness of the alkaline layer decreased. The constant surface pH appears to be the result of active acid and alkali secretion turning on and off in response to changes in luminal pH in tandem with an unstirred layer that modestly slows the movement of acid and alkali equivalents near the tissue surface. The mucus layer at the gastric surface did not appear to play a role in slowing movement of acid/alkali equivalents. The alkaline layer is significantly disrupted when both COX isoforms (COX-1 and COX-2) or the COX-1 isoform alone were inhibited. COX-2 isoform inhibition did not have an effect on surface pH. In conclusion, the protective alkaline layer is the result of COX-1 regulated alkali secretion in tandem with an unstirred layer maintaining a constant surface pH.