The role of cannabinoids in inflammatory modulation of allergic respiratory disorders, inflammatory pain and ischemic stroke
This review is intended to offer updated information on the involvement of cannabinoids in the process of inflammation, focusing on immune/allergic reactions, inflammatory pain and neuroinflammation and discussing the interactions among endocannabinoid metabolism, prostanoids and nitric oxide. Two types of cannabinoid receptors, CB1 and CB2, which belong to the G protein-coupled receptor family, have been identified and are targeted by numerous exogenous and endogenous ligands. The activation of CB2 receptors on mast cells has direct antiinflammatory effects, causing decreased release of pro-inflammatory mediators by these cells. The activation of CB1 receptors on bronchial nerve endings has bronchodilator effects by acting on the airway smooth muscle and may be beneficial in airway hyperreactivity and asthma.
Allergen challenge increases anandamide in bronchoalveolar fluid of patients with allergic asthma
Activation of cannabinoid receptors prevents antigen-induced asthma-like reaction in guinea pigs.
In this study we evaluated the effects of the CB1/CB2 cannabinoid receptor agonist CP55, 940 (CP) on antigen-induced asthma-like reaction in sensitized guinea pigs and we tested the ability of the specific CB2 receptor antagonist SR144528 (SR) and CB1 receptor antagonist AM251 (AM) to interfere with the effects of CP. Ovalbumin-sensitized guinea pigs placed in a respiratory chamber were challenged with the antigen given by aerosol. CP (0.4 mg/kg b.wt.) was given i.p. 3 hrs before ovalbumin challenge. Sixty minutes before CP administration, some animals were treated i.p. with either AM, or SR, or both (0.1 mg/kg b.wt.). Respiratory parameters were recorded and quantified. Lung tissue specimens were then taken for histopathological and morphometric analyses and for eosinophilic major basic protein immunohistochemistry. Moreover, myeloperoxidase activity, 8-hydroxy-2-deoxyguanosine, cyclic adenosine monophosphate (cAMP) and guanosine monophosphate (cGMP) levels, and CB1 and CB2 receptor protein expression by Western blotting were evaluated in lung tissue extracts.
Endogenous cannabinoid receptor agonists inhibit neurogenic inflammations in guinea pig airways
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.
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.
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.
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.
Bronchodilator effect of delta1-tetrahydrocannabinol.
1 delta1-trans-tetrahydrocannabinol, (delta1-THC) produces bronchodilatation in asthmatic patients. 2 Administered in 62 microliter metered volumes containing 50–200 microgram by inhalation from an aerosol device to patients judged to be in a steady state, it increased peak expiratory flow rate (PEFR) and forced expiratory volume in 1 second (FEV1).
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