INHIBITION OF BOMBESIN-STIMULATED ACID-SECRETION BY IMMUNONEUTRALIZATION OF GASTRIN IN DOGS

Bombesin-like peptides stimulate gastrin release and gastric acid secr etion. The increase in gastric acid output is thought to be secondary to gastrin release. A monoclonal antibody (MAb) directed specifically to gastrin (MAb 28.2) was used to study the role of circulating gastri n in the regulation of bombesin-stimulated acid secretion in dogs. Sev en conscious, fasted dogs with gastric fistulas received intravenous b ombesin infusions in fourfold increasing doses from 200 to 3,200 pmol. kg(-1).h(-1). Each dose was given for 45 min. On separate days, dogs w ere pretreated with an intravenous infusion of 7 mg of MAb 28.2 or veh icle (0.1% canine serum albumin). Samples of gastric effluent were col lected by gravity drainage through the gastric fistula, and acid outpu t was measured by titration of gastric effluent to pH 7.0, using 0.2 N NaOH. Plasma gastrin concentrations were determined by radioimmunoass ay. Bombesin infusion produced dose-dependent increases in plasma gast rin concentrations and gastric acid output. Administration of gastrin MAb 28.2 abolished bombesin-stimulated gastric acid output. Immunoneut ralization of circulating gastrin in vivo using a gastrin monoclonal a ntibody in dogs indicates that the acid stimulatory response to bombes in is mediated by gastrin.