Bidirectional control of airway responsiveness by endogenous cannabinoids

A. Calignano, I. Katona, F. Désarnaud, A. Giuffrida, G. La Rana, K. Mackie, T. Freund, D. Piomelli

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

Smoking marijuana or administration of its main active constituent, Δ9-tetrahydrocannabinol (Δ9-THC), may exert potent dilating effects on human airways. But the physiological significance of this observation and its potential therapeutic value are obscured by the fact that some asthmatic patients respond to these compounds with a paradoxical bronchospasm. The mechanisms underlying these contrasting responses remain unresolved. Here we show that the endogenous cannabinoid anandamide exerts dual effects on bronchial responsiveness in rodents: it strongly inhibits bronchospasm and cough evoked by the chemical irritant, capsaicin, but causes bronchospasm when the constricting tone exerted by the vagus nerve is removed. Both effects are mediated through peripheral CB1 cannabinoid receptors found on axon terminals of airway nerves. Biochemical analyses indicate that anandamide is synthesized in lung tissue on calcium-ion stimulation, suggesting that locally generated anandamide participates in the intrinsic control of airway responsiveness. In support of this conclusion, the CB1 antagonist SR141716A enhances capsaicin-evoked bronchospasm and cough. Our results may account for the contrasting bronchial actions of cannabis-like drugs in humans, and provide a framework for the development of more selective cannabinoid-based agents for the treatment of respiratory pathologies.

Original languageEnglish
Pages (from-to)96-101
Number of pages6
JournalNature
Volume408
Issue number6808
DOIs
Publication statusPublished - Nov 2 2000

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Bronchial Spasm
Airway Management
Cannabinoids
rimonabant
Capsaicin
Cough
Marijuana Smoking
Cannabinoid Receptor CB1
Dronabinol
Vagus Nerve
Irritants
Presynaptic Terminals
Cannabis
Rodentia
Ions
Pathology
Calcium
Lung
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • General

Cite this

Calignano, A., Katona, I., Désarnaud, F., Giuffrida, A., La Rana, G., Mackie, K., ... Piomelli, D. (2000). Bidirectional control of airway responsiveness by endogenous cannabinoids. Nature, 408(6808), 96-101. https://doi.org/10.1038/35040576

Bidirectional control of airway responsiveness by endogenous cannabinoids. / Calignano, A.; Katona, I.; Désarnaud, F.; Giuffrida, A.; La Rana, G.; Mackie, K.; Freund, T.; Piomelli, D.

In: Nature, Vol. 408, No. 6808, 02.11.2000, p. 96-101.

Research output: Contribution to journalArticle

Calignano, A, Katona, I, Désarnaud, F, Giuffrida, A, La Rana, G, Mackie, K, Freund, T & Piomelli, D 2000, 'Bidirectional control of airway responsiveness by endogenous cannabinoids', Nature, vol. 408, no. 6808, pp. 96-101. https://doi.org/10.1038/35040576
Calignano A, Katona I, Désarnaud F, Giuffrida A, La Rana G, Mackie K et al. Bidirectional control of airway responsiveness by endogenous cannabinoids. Nature. 2000 Nov 2;408(6808):96-101. https://doi.org/10.1038/35040576
Calignano, A. ; Katona, I. ; Désarnaud, F. ; Giuffrida, A. ; La Rana, G. ; Mackie, K. ; Freund, T. ; Piomelli, D. / Bidirectional control of airway responsiveness by endogenous cannabinoids. In: Nature. 2000 ; Vol. 408, No. 6808. pp. 96-101.
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