Δ9-Tetrahydrocannabinol induces endocannabinoid accumulation in mouse hepatocytes: antagonism by Fabp1 gene ablation
In: Journal of Lipid Research, Jg. 59 (2018), Heft 4, S. 646-657
Online
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Zugriff:
Phytocannabinoids, such as Δ9-tetrahydrocannabinol (THC), bind and activate cannabinoid (CB) receptors, thereby “piggy-backing” on the same pathway's endogenous endocannabinoids (ECs). The recent discovery that liver fatty acid binding protein-1 (FABP1) is the major cytosolic “chaperone” protein with high affinity for both Δ9-THC and ECs suggests that Δ9-THC may alter hepatic EC levels. Therefore, the impact of Δ9-THC or EC treatment on the levels of endogenous ECs, such as N-arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG), was examined in cultured primary mouse hepatocytes from WT and Fabp1 gene-ablated (LKO) mice. Δ9-THC alone or 2-AG alone significantly increased AEA and especially 2-AG levels in WT hepatocytes. LKO alone markedly increased AEA and 2-AG levels. However, LKO blocked/diminished the ability of Δ9-THC to further increase both AEA and 2-AG. In contrast, LKO potentiated the ability of exogenous 2-AG to increase the hepatocyte level of AEA and 2-AG. These and other data suggest that Δ9-THC increases hepatocyte EC levels, at least in part, by upregulating endogenous AEA and 2-AG levels. This may arise from Δ9-THC competing with AEA and 2-AG binding to FABP1, thereby decreasing targeting of bound AEA and 2-AG to the degradative enzymes, fatty acid amide hydrolase and monoacylglyceride lipase, to decrease hydrolysis within hepatocytes.
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Δ9-Tetrahydrocannabinol induces endocannabinoid accumulation in mouse hepatocytes: antagonism by Fabp1 gene ablation
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Autor/in / Beteiligte Person: | McIntosh, Avery L. ; Martin, Gregory G. ; Huang, Huan ; Landrock, Danilo ; Kier, Ann B. ; Schroeder, Friedhelm |
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Zeitschrift: | Journal of Lipid Research, Jg. 59 (2018), Heft 4, S. 646-657 |
Veröffentlichung: | Elsevier, 2018 |
Medientyp: | academicJournal |
ISSN: | 0022-2275 (print) |
DOI: | 10.1194/jlr.M082644 |
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