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

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 secre tion but caused a marked inhibition (80%) of the acid secretion stimulated by pentagastrin (10 mu g/kg, i.v.). The enantiomer WIN 55,212-3 (1-3 mg/kg, i.v.) did not significantly modify basal or pentagastrin-induced acid secr etion. The inhibitory effect of WIN 55,212-2 against pentagastrin was preve nted by the administration of the selective cannabinoid CB1 receptor antago nists SR141716A (1-3 mg/kg, i.v.) and LY320135 (1 mg/kg, i.v.); by contrast , the CB2 receptor antagonist SR144528 (0.3- mg/kg, i.v.) was without effec t. The selective CB2 receptor agonist JWH-015 (0.1-10 mg/kg, i.v.) was inac tive on the increase of acid output stimulated by pentagastrin. These resul ts suggest that the inhibitory effect of WIN 55,212-2 on pentagastrin-stimu lated acid secretion in the anaesthetized rat is mediated by specific canna binoid receptors. Moreover, the antagonism of WIN 55,212-2-induced effects by the selective CB1 receptor antagonists SR141716A and LY320135 together w ith the ineffectiveness of both the CB2 receptor agonist JWH-015 and the CB 2 receptor antagonist SR144528 indicate that CB1 receptor subtypes are pred ominantly involved in the antisecretory effect of WIN 55,212-2.