BOMBESIN PREVENTS GASTRIC INJURY IN THE RAT - ROLE OF GASTRIN

Bombesin or gastrin-releasing peptide prevents gastric injury by an un known mechanism. Since exogenous gastrin is a gastroprotective agent, this study was undertaken to test the hypothesis that gastroprotection by bombesin involves release of endogenous gastrin. Subcutaneous bomb esin (10-100 mu g/kg) dose dependently reduced macroscopic injury to t he acid-secreting portion of the stomach caused by 1 ml of orogastric acidified ethanol (150 mM hydrochloric acid-50% ethanol). Blockade of type A cholecystokinin receptors with intraperitoneal Mk-329 (1 mg/kg) reversed intravenous cholecystokinin (5 nmol/kg)-induced gastroprotec tion, but not that of bombesin. In contrast? intraperitoneal type B ch olecystokinin (gastrin) receptor blockade with L-365,260 (25 mg/kg) di minished the protective actions of both subcutaneous bombesin (100 mu g/kg) and intravenous gastrin (25 pmol/kg). In additional studies, sub cutaneous bombesin (10-100 mu g/kg) dose dependently increased serum g astrin levels (radioimmunoassay). Both the gastroprotective actions of bombesin and bombesin-induced gastrin release were enhanced following immunoneutralization of endogenous somatostatin with intraperitoneal somatostatin antibody (2 mg). These data indicate that bombesin preven ts gastric injury primarily by release of endogenous gastrin and both effects are modified by endogenous somatostatin.