title: The cannabinoid CB2 receptor selective agonist JWH133 reduces mast cell oedema in response to compound 48/80 in vivo but not the release of beta-hexosaminidase from skin slices in vitro.
abstract: In a recent study so far published in abstract form, it was reported that the CB(2) receptor selective agonist AM1241 diminishes oedema produced as a result of mast cell degranulation in vivo. It is, however, not known whether other structurally different CB(2) agonists share this effect, and whether this is due to a direct effect on mast cell function. In the present study, we have investigated the effects of JWH133, a CB(2) receptor selective agonist, together with the anti-inflammatory agent palmitoylethanolamide and its analogue palmitoylisopropylamide, on compound 48/80-induced oedema and degranulation in vivo and in vitro. JWH133 (20 and 200 microg/mouse i.p.) significantly reduced the ability of compound 48/80 to induce oedema in vivo in the anaesthetised mouse following its injection into the ear pinna. Palmitoylethanolamide (200 microg/mouse i.p) also reduced the response to compound 48/80, whereas no firm conclusions could be drawn for palmitoylisopropylamide (20 and 200 microg/mouse i.p.). The CB(2) selective antagonist/inverse agonist SR144528 (60 microg/mouse i.p.) appeared to produce anti-inflammatory effects per se in this model, making it hard to interpret the effects of JWH133 in terms of CB(2) receptor mediated activation. In contrast to the situation in vivo, neither JWH133 (0.3 and 3 microM) nor palmitoylethanolamide (10 microM) affected mast cell degranulation, measured by following the release of the granular protein beta-hexosaminidase, produced by compound 48/80 in vitro in mouse skin slices. The two compounds were also ineffective in inhibiting the binding of [(3)H]pyrilamine to histamine H(1) receptors in vitro. It is concluded that the ability of JWH133 to affect mast cell dependent inflammation in vivo may be mediated by an indirect action upon the mast cells.
authors.affiliation: Department of Pharmacology and Clinical Neuroscience, Umeå University, Sweden. kentolov.jonsson@pharm.umu.se
authors.forename: Kent-Olov
authors.initials: KO
authors.lastname: Jonsson
authors.forename: Emma
authors.initials: E
authors.lastname: Persson
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Fowler
mesh_terms: D000577:Amides; D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D004487:Edema / Q000517:prevention & control*; D063388:Endocannabinoids; D004983:Ethanolamines; D005260:Female; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010169:Palmitic Acids / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D011969:Receptors, Histamine H1 / Q000187:drug effects; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
chemical_list: D000577:Amides; D002186:Cannabinoids; D063388:Endocannabinoids; D004983:Ethanolamines; D010169:Palmitic Acids; D043885:Receptor, Cannabinoid, CB2; D011969:Receptors, Histamine H1; D003189:p-Methoxy-N-methylphenethylamine; C005958:palmidrol; D001619:beta-N-Acetylhexosaminidases; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC