Endogenous cannabinoid receptor agonists inhibit neurogenic inflammations in guinea pig airways

Int Arch Allergy Immunol. 2005 Sep;138(1):80-7. doi: 10.1159/000087361. Epub 2005 Aug 11.


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.

MeSH terms

  • Amides
  • Animals
  • Arachidonic Acids / pharmacology
  • Bronchi / drug effects*
  • Bronchi / innervation
  • Bronchoconstriction / drug effects
  • Calcium Channel Blockers / pharmacology
  • Camphanes / pharmacology
  • Cannabinoid Receptor Agonists*
  • Capsaicin / toxicity
  • Electric Stimulation
  • Endocannabinoids
  • Ethanolamines
  • Guinea Pigs
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Nerve Fibers, Unmyelinated / drug effects*
  • Neurogenic Inflammation / etiology
  • Neurogenic Inflammation / prevention & control*
  • Organ Culture Techniques
  • Palmitic Acids / pharmacology
  • Piperidines / pharmacology
  • Polyunsaturated Alkamides
  • Potassium Channel Blockers / pharmacology
  • Pyrazoles / pharmacology
  • Receptors, Cannabinoid / drug effects*
  • Rimonabant
  • Substance P / biosynthesis
  • Substance P / drug effects


  • Amides
  • Arachidonic Acids
  • Calcium Channel Blockers
  • Camphanes
  • Cannabinoid Receptor Agonists
  • Endocannabinoids
  • Ethanolamines
  • Palmitic Acids
  • Piperidines
  • Polyunsaturated Alkamides
  • Potassium Channel Blockers
  • Pyrazoles
  • Receptors, Cannabinoid
  • SR 144528
  • Substance P
  • palmidrol
  • Rimonabant
  • Capsaicin
  • anandamide