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

Naunyn Schmiedebergs Arch Pharmacol. 1999 Dec;360(6):715-8. doi: 10.1007/s002109900135.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthesia
  • Animals
  • Benzoxazines
  • Camphanes / pharmacology
  • Cannabinoids / antagonists & inhibitors
  • Gastric Acid / metabolism*
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / metabolism
  • Indoles / pharmacology
  • Isomerism
  • Male
  • Morpholines / pharmacology*
  • Naphthalenes / pharmacology*
  • Pentagastrin / antagonists & inhibitors*
  • Pentagastrin / pharmacology*
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Wistar
  • Receptor, Cannabinoid, CB2*
  • Receptors, Cannabinoid
  • Receptors, Drug / agonists*
  • Receptors, Drug / antagonists & inhibitors
  • Rimonabant

Substances

  • Benzoxazines
  • Camphanes
  • Cannabinoids
  • Cnr2 protein, rat
  • Indoles
  • Morpholines
  • Naphthalenes
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB2
  • Receptors, Cannabinoid
  • Receptors, Drug
  • SR 144528
  • Win 55212-2
  • Pentagastrin
  • Rimonabant
  • JHW 015