The cannabinoid CB2 receptor selective agonist JWH133 reduces mast cell oedema in response to compound 48/80 in vivo but not the release of β-hexosaminidase from skin slices in vitro

Palmitoylethanolamide (200 μg/mouse i.p) also reduced the response to compound 48/80, whereas no firm conclusions could be drawn for palmitoylisopropylamide (20 and 200 μg/mouse i.p.). The CB2 selective antagonist/inverse agonist SR144528 (60 μg/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 CB2 receptor mediated activation. In contrast to the situation in vivo, neither JWH133 (0.3 and 3 μM) nor palmitoylethanolamide (10 μM) affected mast cell degranulation, measured by following the release of the granular protein β-hexosaminidase, produced by compound 48/80 in vitro in mouse skin slices. The two compounds were also ineffective in inhibiting the binding of [3H]pyrilamine to histamine H1 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.