| Abstract: | Bombesin or gastrin-releasing peptide preventsgastric injury by an unknown mechanism. Since exogenousgastrin is a gastroprotective agent, this study wasundertaken to test the hypothesis that gastroprotection by bombesin involves release of endogenousgastrin. Subcutaneous bombesin (10-100  g/kg) dosedependently reduced macroscopic injury to theacid-secreting portion of the stomach caused by 1 ml oforogastric acidified ethanol (150 mM hydrochloric acid-50%ethanol). Blockade of type A cholecystokinin receptorswith intraperitoneal MK-329 (1 mg/kg) reversedintravenous cholecystokinin (5 nmol/kg)-inducedgastroprotection, but not that of bombesin. In contrast,intraperitoneal type B cholecystokinin (gastrin)receptor blockade with L-365,260 (25 mg/kg) diminishedthe protective actions of both subcutaneous bombesin(100 mug/kg) and intravenous gastrin (25 pmol/kg). Inadditional studies, subcutaneous bombesin (10-100g/kg) dose dependently increased serum gastrinlevels (radioimmunoassay). Both the gastroprotectiveactions of bombesin and bombesininduced gastrin releasewere enhanced following immunoneutralization ofendogenous somatostatin with intraperitonealsomatostatin antibody (2 mg). These data indicate thatbombesin prevents gastric injury primarily by release ofendogenous gastrin and both effects are modified byendogenous somatostatin. |
