Receptor-independent effects of natural cannabinoids in rat peritoneal mast cells in vitro

AbstractCannabinoids 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 Δ9-tetrahydrocannabinol (Δ9-THC), Δ8-THC, endocannabinoids (anandamide, palmitoylethanolamide) and related compounds (N-decanoyl-, N-lauroyl-, N-myristoyl-, N-stearoyl- and 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 Δ9-THC and Δ8-THC could induce non-lytic, energy- and concentration-dependent histamine releases from RPMC (respective EC50 values: 23.5±1.2; 53.4±20.6 μM, and maxima: 71.2±5.5; 55.7±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 μg/ml). Δ9-THC and Δ8-THC induced in vitro histamine secretion from RPMC through CB receptor-independent interactions, partly involving Gi/o protein activation