The cannabinoid CB 2 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

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 μg/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 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 CB 2 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 CB 2 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 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.