G-protein mediation of cannabinoid-induced phospholipase activation.
The release of arachidonic acid from mouse peritoneal and S49 cells induced by delta 1-tetrahydrocannabinol was found to be altered by prior exposure of the cells to either pertussis toxin or cholera toxin. The stable analogs of GTP and GDP, GTP-gamma-S and GDP-beta-S, were also effective in changing the extent of arachidonate release in saponin-treated cells. GDP-beta-S essentially abolished the THC response, while GTP-gamma-S showed effects mainly on vehicle-treated cells. The cataleptic action of THC in intact mice which is mediated by eicosanoids was also attenuated by pertussis toxin pretreatment. It is suggested that the THC receptor is coupled to phospholipases through one or more G-proteins and that adenylate cyclase probably does not have a role in this mechanism.
Audette
C A
CA
Department of Biochemistry, University of Massachusetts Medical Center, Worcester 01655.
Burstein
S H
SH
Doyle
S A
SA
Hunter
S A
SA
D037361:Adenylate Cyclase Toxin; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002186:Cannabinoids / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced / Q000517:prevention & control; D013759:Dronabinol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D037342:Pertussis Toxin; D010740:Phospholipases / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D002186:Cannabinoids; D012503:Saponins; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D006153:Guanosine Diphosphate; D016718:Arachidonic Acid; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C023427:guanosine 5'-O-(2-thiodiphosphate); D013759:Dronabinol; D037342:Pertussis Toxin; D010740:Phospholipases; D019204:GTP-Binding Proteins