Cannabinoid Receptor Agonists Inhibit Sensory Nerve Activation in Guinea Pig Airways

• Published in: American journal of respiratory and critical care medicine Vol. 170; no. 9; pp. 941 - 946
• Main Authors: Yoshihara, Shigemi, Morimoto, Hiroshi, Yamada, Yumi, Abe, Toshio, Arisaka, Osamu
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 01.11.2004; American Lung Association; American Thoracic Society
• Subjects: Analysis of Variance; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Benzoxazines; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Camphanes - pharmacology; Cannabinoid Receptor Antagonists; Disease Models, Animal; Electric Stimulation; Emergency and intensive respiratory care; Guinea Pigs; Intensive care medicine; Male; Medical sciences; Morpholines - pharmacology; Muscle Contraction - drug effects; Muscle Relaxation - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; Naphthalenes - pharmacology; Neurokinin A; Pharmacology. Drug treatments; Piperidines - pharmacology; Probability; Pyrazoles - pharmacology; Respiratory Muscles - drug effects; Respiratory Muscles - innervation; Rimonabant; Sensitivity and Specificity; Sensory Receptor Cells - drug effects; Maxi-K+ channels; Vertebrata; Intensive care; Mammalia; Guinea pig; Animal; airway; cannabinoid; Rodentia; C-fibers; Resuscitation
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200306-775OC

We examined the effects of cannabinoid receptor agonists on various respiratory reactions induced by the activation of capsaicin-sensitive afferent sensory nerves (C-fibers). (R)-(+)-[2,3-dihydro-5-methyl-3-[(4-merpholino)methyl]pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthyl)methanone (WIN 55212-2) dose-dependently inhibited electrical field stimulation- and capsaicin-induced guinea pig bronchial smooth muscle contraction, but not the neurokinin A-induced contraction. A cannabinoid CB2 receptor antagonist, [N-[(1S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3-carboxamide] (SR 144528), reduced the inhibitory effect of WIN 55212-2, but not a cannabinoid CB1 antagonist, [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride] (SR 141716A). A cannabinoid CB2 agonist, JWH 133, also inhibited electrical field stimulation-induced guinea pig bronchial smooth muscle contraction and its inhibitory effect was blocked by SR 144528. The inhibitory effect of WIN 55212-2 on electrical field stimulation-induced bronchial contraction was reduced by the pretreatment of large conductance Ca(2+)-activated K+ channel (Maxi-K+ channel) blockers, iberiotoxin and charybdotoxin, but not other K+ channel blockers, dendrotoxin or glibenclamide. A Maxi-K+ channel opener, 1-(2'-hydroxy-5'-trifluoromethylphenyl)-5-trifluoromethyl-2(3H)benzimidazolone (NS1619), inhibited bronchial contraction induced by electrical field stimulation. WIN 55212-2 and JWH 133 blocked the capsaicin-induced release of substance P-like immunoreactivity from guinea pig airway tissues. These findings suggest that WIN 55212-2 inhibit the activation of C-fibers via cannabinoid CB2 receptors and Maxi-K+ channels in guinea pig airways.