Endogenous Cannabinoid Receptor Agonists Inhibit Neurogenic Inflammations in Guinea Pig Airways

• Published in: International archives of allergy and immunology Vol. 138; no. 1; pp. 80 - 87
• Main Authors: Yoshihara, Shigemi, Morimoto, Hiroshi, Ohori, Makoto, Yamada, Yumi, Abe, Toshio, Arisaka, Osamu
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.09.2005; S. Karger AG
• Subjects: Animals; Arachidonic Acids - pharmacology; Asthma; Biological and medical sciences; Bornanes - pharmacology; Bronchi - drug effects; Bronchi - innervation; Bronchoconstriction - drug effects; Calcium Channel Blockers - pharmacology; Cannabinoid Receptor Agonists; Capsaicin - toxicity; Electric Stimulation; Endocannabinoids; Ethanolamines; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Guinea Pigs; Immunology; Immunopathology; Male; Medical sciences; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Nerve Fibers, Unmyelinated - drug effects; Neurogenic Inflammation - etiology; Neurogenic Inflammation - prevention & control; Organ Culture Techniques; Original Paper; Palmitic Acids - pharmacology; Piperidines - pharmacology; Polyunsaturated Alkamides; Potassium; Potassium Channel Blockers - pharmacology; Pyrazoles - pharmacology; Receptors, Cannabinoid - drug effects; Rodents; Substance P - biosynthesis; Substance P - drug effects; Maxi-K+ channels; Guinea pig; Cannabinoid; Airway; C fibers; Immunopathology; Agonist; Rodentia; Fiber; Ionic channel; Respiratory system; Respiratory tract; Vertebrata; Immunology; Mammalia; Endogenous; Animal; Inhibitor; Neurogenic inflammation; Biological receptor
• ISSN: 1018-2438; 1423-0097
• DOI: 10.1159/000087361

Background: Although neurogenic inflammation via the activation of C fibers in the airway must have an important role in the pathogenesis of asthma, their regulatory mechanism remains uncertain. Objective: The pharmacological profiles of endogenous cannabinoid receptor agonists on the activation of C fibers in airway tissues were investigated and the mechanisms how cannabinoids regulate airway inflammatory reactions were clarified. Methods: The effects of endogenous cannabinoid receptor agonists on electrical field stimulation-induced bronchial smooth muscle contraction, capsaicin-induced bronchoconstriction and capsaicin-induced substance P release in guinea pig airway tissues were investigated. The influences of cannabinoid receptor antagonists and K + channel blockers to the effects of cannabinoid receptor agonists on these respiratory reactions were examined. Results: Both endogenous cannabinoid receptor agonists, anandamide and palmitoylethanolamide, inhibited electrical field stimulation-induced guinea pig bronchial smooth muscle contraction, but not neurokinin A-induced contraction. A cannabinoid CB2 antagonist, SR 144528, reduced the inhibitory effect of endogenous agonists, but not a cannabinoid CB1 antagonist, SR 141716A. Inhibitory effects of agonists were also reduced by the pretreatment of large conductance Ca 2+ -activated K + channel (maxi-K + channel) blockers, iberiotoxin and charybdotoxin, but not by other K + channel blockers, dendrotoxin or glibenclamide. Anandamide and palmitoylethanolamide blocked the capsaicin-induced release of substance P-like immunoreactivity from guinea pig airway tissues. Additionally, intravenous injection of palmitoylethanolamide dose-dependently inhibited capsaicin-induced guinea pig bronchoconstriction, but not neurokinin A-induced reaction. However, anandamide did not reduce capsaicin-induced guinea pig bronchoconstriction. Conclusions: These findings suggest that endogenous cannabinoid receptor agonists inhibit the activation of C fibers via cannabinoid CB2 receptors and maxi-K + channels in guinea pig airways.