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Br J Pharmacol. 2014 Jun;171(11):2767-77. doi: 10.1111/bph.12597.

Cannabinoids inhibit cholinergic contraction in human airways through prejunctional CB1 receptors.

Author information

1
Laboratoire de Pharmacologie Respiratoire, UPRES EA220, Hôpital Foch, Suresnes, France; Laboratoire de Pharmacologie-Toxicologie, Hôpital Raymond Poincaré, Garches, France.

Abstract

BACKGROUND AND PURPOSE:

Marijuana smoking is widespread in many countries, and the use of smoked synthetic cannabinoids is increasing. Smoking a marijuana joint leads to bronchodilation in both healthy subjects and asthmatics. The effects of Δ(9) -tetrahydrocannabinol and synthetic cannabinoids on human bronchus reactivity have not previously been investigated. Here, we sought to assess the effects of natural and synthetic cannabinoids on cholinergic bronchial contraction.

EXPERIMENTAL APPROACH:

Human bronchi isolated from 88 patients were suspended in an organ bath and contracted by electrical field stimulation (EFS) in the presence of the phytocannabinoid Δ(9) -tetrahydrocannabinol, the endogenous 2-arachidonoylglycerol, the synthetic dual CB1 and CB2 receptor agonists WIN55,212-2 and CP55,940, the synthetic, CB2 -receptor-selective agonist JWH-133 or the selective GPR55 agonist O-1602. The receptors involved in the response were characterized by using selective CB1 and CB2 receptor antagonists (SR141716 and SR144528 respectively).

KEY RESULTS:

Δ(9) -tetrahydrocannabinol, WIN55,212-2 and CP55,940 induced concentration-dependent inhibition of cholinergic contractions, with maximum inhibitions of 39, 76 and 77% respectively. JWH-133 only had an effect at high concentrations. 2-Arachidonoylglycerol and O-1602 were devoid of any effect. Only CB1 receptors were involved in the response because the effects of cannabinoids were antagonized by SR141716, but not by SR144528. The cannabinoids did not alter basal tone or contractions induced by exogenous Ach.

CONCLUSIONS AND IMPLICATIONS:

Activation of prejunctional CB1 receptors mediates the inhibition of EFS-evoked cholinergic contraction in human bronchus. This mechanism may explain the acute bronchodilation produced by marijuana smoking.

KEYWORDS:

bronchi; cannabinoid; cholinergic fibres; humans; muscle contraction; receptors

PMID:
24467410
PMCID:
PMC4243853
DOI:
10.1111/bph.12597
[Indexed for MEDLINE]
Free PMC Article
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