Hirschowitz_1981_Gastroenterology_81_838

We have demonstrated that at doses lower than those used by others in dogs, atropine consistently inhibited food-stimulated gastrin release irrespective of vagal innervation of the stomach. Gastrin release induced by food placed directly into the stomach was studied in four gastric fistula dogs with intact vagi and in three other similar dogs with fundic vagotomy. The studies were repeated in dogs after conversion to truncal vagotomy. Fasting serum gastrin was lower in the intact dogs (33 +/- 1.7 pg/ml) than after fundic vagotomy (61 +/- 13 pg/ml) or truncal vagotomy (97 +/- 20 pg/ml). The same relationship held for absolute postprandial values. However, the integrated gastrin response to food over 2 h was similar in the three groups of dogs (intact 14 +/- 4.6, fundic vagotomy 10.3 +/- 4.3, truncal vagotomy 17.4 +/- 2.4 ng.min/ml). Regardless of the state of gastric vagal innervation atropine 20 microgram/kg . h reduced gastrin releases due to food by 66-76% (p less than 0.05) in all three groups. In small doubling doses (1-16 microgram/kg), atropine given i.v. at 15-min intervals, dose-responsively inhibited food-stimulated gastrin release in the four dogs with intact vagi. Assuming that the atropine effect was cumulative, kinetic analysis of the dose-response data gave a calculated maximum inhibition of 91% and an ID50 of 5.1 microgram/kg or 7.2 X 10-9 mol/kg. Findings of this study indicate a previously undescribed muscarinic cholinergic pathway leading to gastrin release by food.