Receptor-independent effects of natural cannabinoids in rat peritoneal mast cells in vitro.
Cannabinoids can activate CB(1) and CB(2) receptors. Since a CB(2) 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), Delta(8)-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 Delta(9)-THC and Delta(8)-THC could induce non-lytic, energy- and concentration-dependent histamine releases from RPMC (respective EC(50) values: 23.5+/-1.2; 53.4+/-20.6 microM, and maxima: 71.2+/-5.5; 55.7+/-2.7% of the total RPMC histamine content). These were not blocked by CB(1) (SR141716A) or CB(2) (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 microg/ml). Delta(9)-THC and Delta(8)-THC induced in vitro histamine secretion from RPMC through CB receptor-independent interactions, partly involving G(i/o) protein activation.
Bueb
J L
JL
Neuroimmunology and Inflammation, Centre de Recherche Public-Santé, Luxembourg, Belgium. jean-luc.bueb@crp-sante.lu
Lambert
D M
DM
Tschirhart
E J
EJ
D000577:Amides; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001548:Benzalkonium Compounds / Q000494:pharmacology; D048588:Benzoxazines; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids / Q000138:chemical synthesis / Q000494:pharmacology*; D002478:Cells, Cultured; D013759:Dronabinol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D063388:Endocannabinoids; D004983:Ethanolamines; D006636:Histamine Release; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010169:Palmitic Acids / Q000494:pharmacology; D010537:Peritoneum / Q000166:cytology / Q000187:drug effects*; D053284:Polyunsaturated Alkamides; D051381:Rats; D017208:Rats, Wistar; D003189:p-Methoxy-N-methylphenethylamine
D000577:Amides; D001095:Arachidonic Acids; D001548:Benzalkonium Compounds; D048588:Benzoxazines; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids; D004983:Ethanolamines; D009025:Morpholines; D009281:Naphthalenes; D010169:Palmitic Acids; D053284:Polyunsaturated Alkamides; D003189:p-Methoxy-N-methylphenethylamine; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C005958:palmidrol; D013759:Dronabinol; C078814:anandamide