Cannabinoid CB2 Receptor Activation Prevents Bronchoconstriction And Airway Oedema

[Julie Gardener]

Cannabinoid CB2 receptor activation prevents bronchoconstriction and airway oedema in a model of gastro-oesophageal reflux​

Yong-Yao Cuia, b, Bruno D'Agostinoc, Paul-André Rissea, Guiseppina Marroccoc, Emmanuel Nalinea, , , Yong Zhangb, Hong-Zhuan Chenb, Olivier Financed, Murielle Rinaldi-Carmonae, Francesco Rossic and Charles Adveniera
aUniversité Versailles St-Quentin, UPRES EA220, Pharmacology, Foch Hospital, 11, rue Guillaume Lenoir, 92150 Suresnes, France
bDepartment of Pharmacology, College of Basic Medical Sciences, Shanghai JiaoTong University, 280 South Chongqing Road, Shanghai 200025, China
cDepartment of Experimental Medicine – Section of Pharmacology, Faculty of Medicine and Surgery, 2nd University of Naples, Via Constantinopoli 16, 80138 Naples, Italy
dSanofi-Aventis Recherche, 371 rue J Blayac, 34184 Montpellier, France
eSanofi-Aventis Recherche, 194 route d'Espagne, 31036 Toulouse, France
Received 7 April 2006; revised 1 June 2007; accepted 12 June 2007. Available online 3 July 2007.

European Journal of Pharmacology
Volume 573, Issues 1-3, 14 November 2007, Pages 206-213

Abstract

Cannabinoids have been shown to inhibit sensory nerve activation in guinea-pigs and humans. Their effects are mediated by specific activation of two types of receptors, named CB1 and CB2. The purpose of this study was to investigate the effects of WIN 55,212-2, (R)-(+)-[2,3-dihydro-5methyl-3-[(4-morpholino)methyl]pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthyl)methanone, a non selective agonist of cannabinoid receptors, and JWH 133, (6aR,10aR)-3-(1,1-dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran a selective cannabinoid CB2 receptor agonist, on the sensory nerve component of intraoesophageal (i.oe.) HCl-induced airway microvascular leakage and bronchoconstriction in guinea-pigs. We also tested the effect of WIN 55,212-2 on substance P-induced plasma extravasation and bronchoconstriction. Airway microvascular leakage and bronchoconstriction induced by i.oe. HCl was inhibited by the cannabinoid CB1/CB2 agonist WIN 55,212-2 (0.3—3 mg/kg i.p.) in a dose-dependent manner (maximal inhibition at the dose of 3 mg kg− 1, P < 0.01). The effect of WIN 55,212-2 was inhibited by a cannabinoid CB2 receptor antagonist SR 144528, [N-[(1S)-endo-1,3,3-trimethylbicyclo[2,2,1] heptan-2yl]-5-(-4-chloro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3-carboxamide], but not by a CB1 receptor antagonist, SR 141716, [N-(piperidin-1yl)-5-(-4-chlorophenyl)-1-(2,4dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride]. The cannabinoid CB2 agonist JWH 133 (0.3—3 mg/kg i.p.) mimicked the inhibitory effect of WIN 55,212-2 on HCl-induced microvascular leakage. Under similar conditions, WIN 55,212-2 (1 mg kg − 1 i.p.) was unable to counteract the airway microvascular leakage and bronchoconstriction induced by substance P. These results suggest that inhibition by WIN 55,212-2 of airway plasma extravasation and bronchoconstriction induced by i.oe. HCl instillation in guinea-pigs is mediated through cannabinoid CB2 receptor activation.

Source: ScienceDirect - European Journal of Pharmacology : Cannabinoid CB2 receptor activation prevents bronchoconstriction and airway oedema in a model of gastro-oesophageal reflux