EFFECT OF A BOMBESIN ANTAGONIST ON OMEPRAZOLE-INDUCED GASTRIN-SECRETION IN RATS

The physiological role of gastrin-releasing peptide in the regulation of gastrin release was investigated by examining the effects of a bomb esin analog, [D-Phe(6)](delete) bombesin (6-13)-methyl-ester (BME), on gastrin secretion stimulated by bombesin or by omeprazole-induced gas tric neutralization in the rat. Bombesin-induced gastrin secretion was inhibited in a dose-related manner by subcutaneous injection of BME; inhibition was significant (p < 0.05) at a BME dose of 0.5 mg/kg. BME alone induced a small, but significant, increase in plasma gastrin con centration. Oral administration of omeprazole induced a marked increas e in plasma gastrin concentration, which was inhibited significantly b y BME. Rats treated with omeprazole, BME, or both drugs showed no appa rent quantiative differences in antral gastrin mRNA abundance. These r esults indicate that BME is a potent competitive antagonist of bombesi n-induced antral gastrin secretion, but also exhibits partial-agonist activity. Furthemore, endogenous GRP appears to contribute to stimulat ion of gastrin secretion in response to omeprazole-induced gastric neu tralization.