Mechanism of intragastric tetramethylammonium protection against 40% ethanol injury in rat stomach

Abstract

The effect of tetramethylammonium (TMA), a ganglionic stimulant, on gastric mucosal injury induced by 40% ethanol was examined. In studies I–III, rats were treated with intragastric vehicle or TMA (1 or 10 mg/kg). In study I, 1 hr after the treatment, 40% ethanol was given intragastrically. The length of the linear corpus mucosal lesions was measured unbiasedly with a caliper after another hour. In study II, mean blood pressure was assessed before and after the treatment. In study III, 1 hr after the treatment, gastric mucus and juice volumes, and titratable acid were measured. In study IV, 40% ethanol (10 ml/kg) was administered intragastrically immediately after 0.2 or 1.4 ml of intragastric vehicle treatment. One hour later, gastric lesion score was assessed as in study I. Results show that (1) intragastric TMA dose-dependently protected against 40% ethanol-induced gastric injury; (2) neither dose of intragastric TMA increased mean blood pressure; (3) there was a dose-related increase in gastric mucus secretion for TMA 1 and 10 mg/kg, and a significant increase in gastric juice volume only for TMA 10 mg/kg; and (4) the rats treated with 1.4. ml of vehicle plus 40% ethanol had significantly less injury than those treated with 0.2 ml of vehicle plus 40% ethanol. We conclude that the protective effect of intragastric TMA can be explained by its dose-related effect in enhancing gastric mucus secretion for TMA 1 and 10 mg/kg and the significantly greater increase in gastric juice volume for TMA 10 mg/kg. Even though parenteral TMA is a recognized ganglionic stimulant, the protective effect of intragastric TMA is unlikely to be due to its ganglionic stimulatory property, as neither 1 nor 10 mg/kg intragastric TMA increases mean blood pressure. However, the possibility that intragastric TMA acts as a local stimulant of intramural ganglia cannot be excluded.