Pharmacological analysis of cannabinoid-induced inhibition of gastric mucosal damage and gastric motility

Abstract

Aims: Cannabinoid receptors are likely to be involved in different gastrointestinal functions: Δ9-tetrahydrocannabinol inhibits stress ulcer (Sofia et al., 1978), decreases intragastric pressure and the pyloric contractility (Krowicki et al.,1999) and CB1 receptor agonists decrease the gastric acid secretion (Adami et al., 2002). We aimed to detect the effect of endogenous cannabinoids (anandamide and methanadamide) and the synthetic analogue WIN-552, 212–2 on acid-independent ulcer model and stimulated gastric motility. Gastric mucosal damage was induced by acidified ethanol in rats. Gastric motility was tested by using the balloon method as described by LeFebvre et al.(1992) in the rats. Gastric motility was stimulated centrally by insulin (5 IU). The substances were given intravenously (i.v.) and intracerebroventricularly (i.c.v.). Results: It was found that: 1. Anandamide, methanandamide (1.3–5.2µmol/kg i.v.) and WIN-552,212–2 (0.09–0.2µmol/kg i.v.) inhibited the ethanol-induced gastric mucosal damage in a significant manner. Anandamide and methanandamide given i.c.v. inhibited the mucosal lesions in the doses range of 12.5–110 nmol/rat. 2. The gastro-protective effect of methanandamide was antagonized by the cannabinoid CB1 receptor antagonist SR 141716A as well as by the vanilloid receptor antagonist capsazepine, indicating that both CB1 and TRPV1 receptors may be involved in gastroprotective effect of cannabinoid receptor stimulants. 3. The µinsulin-induced enhanced gastric motor activity was reduced by anadamide and methanandamide (1.3–5.2µmol/kg, i.v.). This effect was reversed by SR 141716A (4.32µmol/kg, i.v.), but was only partially inhibited by capsazepine. Conclusion: 1. Cannabinoid CB1 receptors are likely to be involved in gastric mucosal defense. 2. Activation of CB1 receptors results in inhibition of stimulated gastric motor activity. 3. TRPV1 receptors may be involved in the gastroprotective effect of methanandamid, but only partially in the inhibition of gastric motility. The work was supported by ETT Grant 529