Receptor-independent e¡ects of natural cannabinoids in rat peritoneal mast cells in vitro

Cannabinoids can activate CB1 and CB2 receptors. Since a CB2 mRNA has been described in rat peritoneal mast cells (RPMC), we investigated a series of cannabinoids and derivatives for their capacity to stimulate RPMC. Effects of natural cannabinoids v9-tetrahydrocannabinol (v9-THC), v8-THC, endocannabinoids (anandamide, palmitoylethanolamide) and related compounds (N-decanoyl-, N-lauroyl-, N-myristoyl-, N-stearoyland N-oleoyl-ethanolamines; N-palmitoyl derivatives (-butylamine, -cyclohexylamine, -isopropylamine) ; and N-palmitoyl, O-palmitoylethanolamine), and synthetic cannabinoids including WIN 55,212-2, SR141716A and SR144528 were assessed for their capacity to induce histamine release or prime RPMC stimulated by compound 48/80. Only v9-THC and v8-THC could induce non-lytic, energyand concentration-dependent histamine releases from RPMC (respective EC50 values: 23.5 þ 1.2; 53.4 þ 20.6 WM, and maxima: 71.2 þ 5.5; 55.7 þ 2.7% of the total RPMC histamine content). These were not blocked by CB1 (SR141716A) or CB2 (SR144528) antagonists, but reduced by pertussis toxin (100 ng/ml). Endocannabinoids and analogues did neither induce histamine secretion, nor prime secretion induced by compound 48/80 (0.2 Wg/ml). v9-THC and v8-THC induced in vitro histamine secretion from RPMC through CB receptor-independent interactions, partly involving Gi=o protein activation. ß 2001 Elsevier Science B.V. All rights reserved.