Bombesin-induced gastroprotection

Abstract

Bombesin is an endogenous gut peptide that is prominent in the stomach. In addition to its effects on modulating acid and gut peptide secretion, recent evidence indicates that bombesin is a potent gastroprotective agent. This review article examines the ability of bombesin to prevent gastric injury. Its protective actions appear to be mediated primarily via the release of endogenous gastrin, as gastroprotection is negated by blockade of gastrin receptors. Bombesin-induced gastroprotection and gastrin release are modified by somatostatin. Immunoneutralization of endogenous somatostatin increases the ability of bombesin to prevent gastric injury by increasing gastrin release. In mechanistic studies, ablation of capsaicin-sensitive afferent neurons abolishes bombesin-induced gastroprotection while cyclo-oxygenase inhibition partially reverses this effect. Nitric oxide synthase inhibition also negates bombesin-induced gastroprotection as well as the ability of bombesin to increase gastric mucosal blood flow. Taken together, the available evidence indicates that bombesin causes release of endogenous gastrin that activates sensory neurons located in the gastric mucosa. Activation of sensory neurons causes increased production of nitric oxide through activation of constitutive nitric oxide synthase, which leads to a resultant increase in gastric mucosal blood flow and renders the stomach less susceptible to damage from luminal irritants.

FIGURE 1. Effect of intraperitoneal type B CCK/gastrin receptor blockade (L-365,260) given 30 minutes before a 30-minute subcutaneous pretreatment with saline or bombesin (100 μg/kg) or a 10-minute intravenous treatment with gastrin-17 (25 pmol/kg) on macroscopic gastric injury from acidified ethanol; expressed as mean ± standard error of mean, n ≥ 5 for all groups. *P < 0.05 versus saline counterpart. +P < 0.05 versus vehicle/gastrin. #P < 0.05 versus vehicle/bombesin.

FIGURE 2. Effect of nitric oxide synthase inhibition with subcutaneous l-NAME (10 mg/kg) and the effect of l-NAME combined with intraperitoneal l-arginine (l-Arg; 300 mg/kg) or d-arginine (d-Arg; 300 mg/kg) on bombesin (100 μg/kg)-induced gastric hyperemia. Data are presented as percent change from baseline blood flow determinations and represent the mean ± SEM; n ≥ 5/group. *P < 0.05 versus saline counterpart. +P < 0.05 versus saline/bombesin. #P < 0.05 versus l-NAME/bombesin.

FIGURE 3. Schematic representation of mechanism(s) responsible for bombesin-induced gastroprotection.