Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P21554 (cannabinoid receptor)
 3,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endocannabinoids (ECs) and cannabinoids are very lipophilic molecules requiring the presence of cytosolic binding proteins that chaperone these molecules to intracellular targets. While three different fatty acid binding proteins (FABP3, -5, and -7) serve this function in brain, relatively little is known about how such hydrophobic ECs and cannabinoids are transported within the liver. The most prominent hepatic FABP, liver fatty acid binding protein (FABP1 or L-FABP), has high affinity for arachidonic acid (ARA) and ARA-CoA, suggesting that FABP1 may also bind ARA-derived ECs (AEA and 2-AG). Indeed, FABP1 bound ECs with high affinity as shown by displacement of FABP1-bound fluorescent ligands and by quenching of FABP1 intrinsic tyrosine fluorescence. FABP1 also had high affinity for most non-ARA-containing ECs, FABP1 inhibitors, EC uptake/hydrolysis inhibitors, and phytocannabinoids and less so for synthetic cannabinoid receptor (CBR) agonists and antagonists. The physiological impact was examined with liver from wild-type (WT) versus FABP1 gene-ablated (LKO) male mice. As shown by liquid chromatography and mass spectrometry, FABP1 gene ablation significantly increased hepatic levels of AEA, 2-AG, and 2-OG. These increases were not due to increased protein levels of EC synthetic enzymes (NAPEPLD and DAGL) or a decreased level of EC degradative enzyme (FAAH) but correlated with complete loss of FABP1, a decreased level of SCP2 (8-fold less prevalent than FABP1, but also binds ECs), and a decreased level of degradative enzymes (NAAA and MAGL). These data indicated that FABP1 not only is the most prominent endocannabinoid and cannabinoid binding protein but also impacts hepatic endocannabinoid levels.
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PMID:FABP1: A Novel Hepatic Endocannabinoid and Cannabinoid Binding Protein. 2755 86

The endocannabinoid system is currently under intense investigation due to the therapeutic potential of cannabinoid-based drugs as treatment options for a broad variety of diseases including cancer. Besides the canonical endocannabinoid system that includes the cannabinoid receptors CB1 and CB2 and the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol, recent investigations suggest that other fatty acid derivatives, receptors, enzymes, and lipid transporters likewise orchestrate this system as components of the endocannabinoid system when defined as an extended signaling network. As such, fatty acids acting at cannabinoid receptors (e.g. 2-arachidonoyl glyceryl ether [noladin ether], N-arachidonoyldopamine) as well as endocannabinoid-like substances that do not elicit cannabinoid receptor activation (e.g. N-palmitoylethanolamine, N-oleoylethanolamine) have raised interest as anticancerogenic substances. Furthermore, the endocannabinoid-degrading enzymes fatty acid amide hydrolase and monoacylglycerol lipase, lipid transport proteins of the fatty acid binding protein family, additional cannabinoid-activated G protein-coupled receptors, members of the transient receptor potential family as well as peroxisome proliferator-activated receptors have been considered as targets of antitumoral cannabinoid activity. Therefore, this review focused on the antitumorigenic effects induced upon modulation of this extended endocannabinoid network.
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PMID:Targeting the endocannabinoid system as a potential anticancer approach. 2939 Aug 96

Hepatic endocannabinoids (EC) and their major binding/"chaperone" protein (i.e., liver fatty acid binding protein-1 [FABP1]) are associated with development of nonalcoholic fatty liver (NAFLD) in animal models and humans. Since expression of the highly prevalent human FABP1 T94A variant induces serum lipid accumulation, it is important to determine its impact on hepatic lipid accumulation and the EC system. This issue was addressed in livers from human subjects expressing only wild-type (WT) FABP1 T94T (TT genotype) or T94A variant (TC or CC genotype). WT FABP1 males had lower total lipids (both neutral cholesteryl esters, triacylglycerols) and phospholipids than females. WT FABP1 males' lower lipids correlated with lower levels of the N-acylethanolamide DHEA and 2-monoacylglycerols (2-MAG) (2-OG, 2-PG). T94A expression in males increased the hepatic total lipids (triacylglycerol, cholesteryl ester), which is consistent with their higher level of CB1-potentiating 2-OG and lower antagonistic EPEA. In contrast, in females, T94A expression did not alter the total lipids, neutral lipids, or phospholipids, which is attributable to the higher cannabinoid receptor-1 (CB1) agonist arachidonoylethanolamide (AEA) and its CB1-potentiator OEA being largely offset by reduced potentiating 2-OG and increased antagonistic EPEA. Taken together, these findings indicate that T94A-induced alterations in the hepatic EC system contribute at least in part to the hepatic accumulation of lipids associated with NAFLD, especially in males.
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PMID:Human Liver Fatty Acid Binding Protein-1 T94A Variant, Nonalcohol Fatty Liver Disease, and Hepatic Endocannabinoid System. 2948 37