Cannabinoid CB1 Receptors Mediate the Gastroprotective Effect of Neurotensin

Several lines of evidence indicate that neuropeptides exhibit protective properties against gastroduodenal ulcers. Neurotensin, a gut-brain neuropeptide, is implicated in a number of physiological processes in the central nervous system and peripheral tissues including gastrointestinal tract. In the present study, we aimed to investigate the gastroprotective potential of either peripherally or centrally administered neurotensin with a look at the role of the cannabinoid CB1 receptors which are located in brain areas implicated in the regulation of gastric functions.

Gastric mucosal damage was induced by intragastric administration of acidified ethanol in male Wistar rats. One hour later, gastric lesions were evaluated macroscopically. In gastroprotection study, neurotensin was administered either intravenously (1.5, 3, and 5 µM/kg) or intracerebroventricularly (0.5, 1, and 2.5 nM/rat) 30 min before the ethanol challenge. In order to evaluate the involvement of central CB1 receptors in the gastroprotective effect of neurotensin, the CB1 receptor antagonist AM251 (5, 10, and 15 nM/rat) was given i.c.v. 30 min prior to the administration of neurotensin. The effects of AM251 on the intact stomach and ethanol-induced gastric lesions were also evaluated.

Acidified ethanol induced large areas of gastric lesions which were significantly reduced by the highest dose of neurotensin in i.v. or i.c.v. application. The gastroprotective effect of neurotensin was prevented by pretreatment with 15 nM/rat AM251. AM251 had no effect by itself.

Peripherally or centrally given neurotensin protects gastric mucosa against damage induced by acidified ethanol through the activation of central cannabinoid CB1 receptors.