Effects of indomethacin, aspirin and related compounds on the transgastric potential difference in cats

Indomethacin was effective orally (intragastrically) and intravenously at 5 mg/kg in producing decreases in the transgastric electrical potential difference of anesthetized cats. The onset of action was, however, delayed as compared with direct irritants administered intragastrically such as salicylic acid. Aspirin administered intragastrically at 50 mg/kg caused a biphasic effect, an initial rapid drop followed by partial recovery after washout and then a subsequent slow decline similar to that observed after intravenous administration of the same dose. The effects of intragastric indomethacin were prevented by the concomitant topical administration of prostaglandin E2 while those of aspirin were only attenuated. The results are consistent with a prostaglandin mechanism (depletion) for the gastric mucosal effects of indomethacin. Aspirin, on the other hand, may have a direct irritant effect on the gastric mucosa as well as acting as an inhibitor of prostaglandin synthetase (cyclooxygenase).