Stimulation of anandamide biosynthesis in N-18TG2 neuroblastoma cells by delta 9-tetrahydrocannabinol (THC).
A concentration-related stimulation of anandamide (arachidonylethanolamide) synthesis by delta 9-tetrahydrocannabinol (THC) was observed in N-18TG2 neuroblastoma cells. Anandamide was detected and measured using an approach in which [3H]arachidonic acid and [14C]ethanolamine were incorporated into the phospholipids of subconfluent monolayers of cells, and the radiolabeled products were analyzed by TLC following agonist exposure. Both precursors showed similar concentration-response relationships and time dependencies consistent with the production of a product containing both the ethanolamine and arachidonyl moieties. The radiolabeled product also migrated together with authentic anandamide on two-dimensional TLC, confirming its identity as arachidonylethanolamide. Approximately two-thirds of the observed synthesis could be inhibited by 1 microM wortmannin, an agent previously reported to inhibit THC-stimulated arachidonic acid release. These findings are in agreement with reports showing that THC can mobilize phospholipid bound arachidonic acid, leading to the production of other eicosanoids.
Burstein
S H
SH
Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01655.
Hunter
S A
SA
D016718:Arachidonic Acid / Q000378:metabolism; D001095:Arachidonic Acids / Q000096:biosynthesis*; D002855:Chromatography, Thin Layer; D013759:Dronabinol / Q000494:pharmacology*; D063388:Endocannabinoids; D019856:Ethanolamine; D004983:Ethanolamines / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D053284:Polyunsaturated Alkamides; D014407:Tumor Cells, Cultured
D001095:Arachidonic Acids; D063388:Endocannabinoids; D004983:Ethanolamines; D053284:Polyunsaturated Alkamides; D016718:Arachidonic Acid; D019856:Ethanolamine; D013759:Dronabinol; C078814:anandamide