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 microg/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.

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“…At high doses, THC decreased histamine-induced gastric acid secretion in isolated stomach preparations 432 (Rivas-V and Garcia, 1980) and in pylorus-ligated rats (Sofia et al, 1978). Pentagastrin-induced gastric acid secretion was also inhibited by HU-210 and WIN 55,212-2, an effect that could be prevented by CB 1 blockade (Coruzzi et al, 1999;Adami et al, 2002). These studies suggest a role for CB 1 receptors located on preganglionic and postganglionic cholinergic pathways in the regulation of gastric acid secretion.…”

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Inhibition of Monoacylglycerol Lipase Attenuates Nonsteroidal Anti-Inflammatory Drug-Induced Gastric Hemorrhages in Mice

“…Gastric acid secretion by parietal cells in the gastric fundus can be stimulated neuronally or hormonally, by histamine (paracrine) or gastrin (endocrine) (Schubert, 2008). Although the synthetic cannabinoid agonists (6aR)-trans-3-(1,1-dimethylheptyl)-6a,7,10,10a-tetrahydro-1-hydroxy-6,6-dimethyl-6H-dibenzo [b,d]pyran-9-methanol (HU-210) and WIN55,212-2 had no effect on basal stomach acid production in rats, each compound blocked pentagastrin-induced acid secretion (Coruzzi et al, 1999;Adami et al, 2002). However, neither compound affected histamine-induced acid production, suggesting a systemic endocrine mechanism of acid modulation, not direct tissue stimulation (Adami et al, 2002).…”