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The role of lipid rafts in the biosynthesis and recycling of endogenous cannabinoids
Author(s) -
Terebova Ekaterina A,
Barker Eric L
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1177-b
Subject(s) - ionomycin , anandamide , lipid raft , endocannabinoid system , endocytosis , chemistry , microbiology and biotechnology , cannabinoid receptor , phospholipase d , endogeny , lipid signaling , cannabinoid , biochemistry , cell , biology , signal transduction , receptor , intracellular , agonist
The endogenous cannabinoids anandamide (AEA) and 2‐arachidonylglycerol (2‐AG) mimic delta 9 ‐tetrahydrocannabinol (Δ 9 ‐THC) a plant‐derived cannabinoid. The mechanisms of AEA and 2‐AG biosynthesis are not completely understood. We hypothesize that AEA can be recycled by the cell to form new AEA and 2‐AG molecules. Furthermore, we hypothesize that AEA and 2‐AG are synthesized in and released from the lipid raft/caveolae microdomains in RBL‐2H3 cells. When the lipid raft organization was disrupted in RBL‐2H3 cells, the synthesis and release of AEA and 2AG was attenuated in response to stimulation with ionomycin. We also discovered that the synthesis of AEA may take place independent of N‐acyl phosphatidylethanolamine phospholipase D (NAPE PLD). In a different set of experiments, we pursued the possibility that the cell may utilize calcium as a “switch” by which the synthesis of AEA is triggered and the endocytosis of AEA is simultaneously disrupted. We discovered that in the presence of ionomycin, the uptake of AEA was reduced in RBL‐2H3 cells. Our findings suggest a mechanism consistent with calcium‐modulated activation of AEA synthesis and simultaneous termination of the uptake. Together these data suggest that the synthesis and release of AEA and 2‐AG take place in the lipid raft/caveolae microdomains in RBL‐2H3 cell, independent of NAPE PLD. This research was supported by grant R21 DA018112 from NIH.