title: Endogenous cannabinoid receptor agonists inhibit neurogenic inflammations in guinea pig airways.
abstract: 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 Ca2+ -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.
authors.affiliation: Department of Pediatrics, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi 321-0293, Japan. shigemi@dokkyomed.ac.jp
authors.forename: Shigemi
authors.initials: S
authors.lastname: Yoshihara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morimoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohori
authors.forename: Yumi
authors.initials: Y
authors.lastname: Yamada
authors.forename: Toshio
authors.initials: T
authors.lastname: Abe
authors.forename: Osamu
authors.initials: O
authors.lastname: Arisaka
mesh_terms: D000577:Amides; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects* / Q000294:innervation; D016084:Bronchoconstriction / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D001892:Camphanes / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists; D002211:Capsaicin / Q000633:toxicity; D004558:Electric Stimulation; D063388:Endocannabinoids; D004983:Ethanolamines; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects*; D020078:Neurogenic Inflammation / Q000209:etiology / Q000517:prevention & control*; D009924:Organ Culture Techniques; D010169:Palmitic Acids / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043882:Receptors, Cannabinoid / Q000187:drug effects*; D000077285:Rimonabant; D013373:Substance P / Q000096:biosynthesis / Q000187:drug effects
chemical_list: D000577:Amides; D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D001892:Camphanes; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; D004983:Ethanolamines; D010169:Palmitic Acids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D026902:Potassium Channel Blockers; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; C110630:SR 144528; D013373:Substance P; C005958:palmidrol; D000077285:Rimonabant; D002211:Capsaicin; C078814:anandamide