Inhibitory effect of the cannabinoid receptor agonist WIN 55,212-2 on pentagastrin-induced gastric acid secretion in the anaesthetized rat

Abstract.

The effect of the cannabinoid (CB) receptor agonist WIN 55,212-2 on gastric acid secretion was studied in the anaesthetized rat after stimulation with pentagastrin. WIN 55,212-2 (0.5–2 mg/kg, i.v.) was inactive on basal secretion but caused a marked inhibition (80%) of the acid secretion stimulated by pentagastrin (10 µg/kg, i.v.). The enantiomer WIN 55,212-3 (1–3 mg/kg, i.v.) did not significantly modify basal or pentagastrin-induced acid secretion. The inhibitory effect of WIN 55,212-2 against pentagastrin was prevented by the administration of the selective cannabinoid CB₁ receptor antagonists SR141716A (1 mg/kg, i.v.) and LY320135 (1 mg/kg, i.v.); by contrast, the CB₂ receptor antagonist SR144528 (0.3–1 mg/kg, i.v.) was without effect. The selective CB₂ receptor agonist JWH-015 (0.1–10 mg/kg, i.v.) was inactive on the increase of acid output stimulated by pentagastrin. These results suggest that the inhibitory effect of WIN 55,212-2 on pentagastrin-stimulated acid secretion in the anaesthetized rat is mediated by specific cannabinoid receptors. Moreover, the antagonism of WIN 55,212-2-induced effects by the selective CB₁ receptor antagonists SR141716A and LY320135 together with the ineffectiveness of both the CB₂ receptor agonist JWH-015 and the CB₂ receptor antagonist SR144528 indicate that CB₁ receptor subtypes are predominantly involved in the antisecretory effect of WIN 55,212-2.