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.