Effects of compounds chemically related to salicylate on isolated antral mucosa of rabbits.

This study examines some of the gastric mucosal effects of compounds structurally related to salicylate (which consists of a hydroxyl and a carboxyl group attached to a benzene ring) in order to determine the importance of the various ligands of the salicylate molecule. The presence of carboxyl group increases mucosal permeability to acid. This increase in cation flow initially is associated with a decrease in anion permeability. These ion selective effects subsequently give way to a nonspecific increase in permeability. The presence of a carboxyl group also is associated with a more than 80% decrease in short circuit current. A similar decrease in short circuit current occurs when the mucosa is exposed to a pyridine molecule with an attached carboxyl group (pyridine-3-carboxylic acid), but in a relatively low concentration, this agent also decreases the back diffusion of acid. The above noted changes in mucosal permeability and short circuit current do not appear to be attributable to the benzene or phenolic ligands of the salicylate molecule. It is concluded that the presence of a sufficient concentration of an exposed carboxyl group on the mucosal side of the tissue causes an increase in the permeability of the mucosa to acid. The presence of a carboxyl group also appears to alter active ion transport, but this effect cannot be attributed to enhanced diffusion of acid into the tissue. The data implicate the carboxyl group of salicylate as being key to its damaging effects on the stomach.