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

Cannabinoids can activate CB! and CBI 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 Delta (9)-tetrahydrocannabinol (Delta (9)-THC), Del ta (8)-THC, endocannabinoids (anandamide, palmitoylethanolamide) and relate d compounds (N-decanoyl-, N-lauroyl-, N-myristoyl-, N-stearoyl- and N-oleoy l-ethanolamines; N-palmitoyl derivatives (-butylamine, -cyclohexylamine, -i sopropylamine); and N-palmitoyl, O-palmitoylethanolamine), and synthetic ca nnabinoids including WIN 55,212-2, SR141716A and SR144528 were assessed for their capacity to induce histamine release or prime RPMC stimulated by com pound 48/80. Only Delta (9)-THC and Delta (8)-THC could induce non-lytic, e nergy- and concentration-dependent histamine releases from RPMC (respective EC50 values: 23.5 +/-1.2; 53.4 +/- 20.6 muM, and maxima: 71.2 +/-5.51 55.7 +/-2.7% of the total RPMC histamine content). These were not blocked by CB 1 (SR141716A) or CB2 (SR144528) antagonists, but reduced by pertussis toxin (100 ng/ml). Endocannabinoids and analogues did neither induce histamine s ecretion, nor prime secretion induced by compound 48/80 (0.2 mug/ml). Delta (9)-THC and Delta (8)-THC induced in vitro histamine secretion from RPMC t hrough CB receptor-independent interactions, partly involving G(i/o) protei n activation. (C) 2001 Elsevier Science B.V. All rights reserved.