The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Fatty Acid-binding Proteins Transport N-Acylethanolamines to Nuclear Receptors and Are Targets of Endocannabinoid Transport Inhibitors
Open accessAbstract
N-acylethanolamines (NAEs) are bioactive lipids that engage diverse receptor systems. Recently, we identified fatty acid-binding proteins (FABPs) as intracellular NAE carriers. Here, we provide two new functions for FABPs in NAE signaling. We demonstrate that FABPs mediate the nuclear translocation of the NAE oleoylethanolamide, an agonist of nuclear peroxisome proliferator-activated receptor α (PPARα). Antagonism of FABP function through chemical inhibition, dominant-negative approaches, or shRNA-mediated knockdown reduced PPARα activation, confirming a requisite role for FABPs in this process. In addition, we show that NAE analogs, traditionally employed as inhibitors of the putative endocannabinoid transmembrane transporter, target FABPs. Support for the existence of the putative membrane transporter stems primarily from pharmacological inhibition of endocannabinoid uptake by such transport inhibitors, which are widely employed in endocannabinoid research despite lacking a known cellular target(s). Our approach adapted FABP-mediated PPARα signaling and employed in vitro binding, arachidonoyl-[1-(14)C]ethanolamide ([(14)C]AEA) uptake, and FABP knockdown to demonstrate that transport inhibitors exert their effects through inhibition of FABPs, thereby providing a molecular rationale for the underlying physiological effects of these compounds. Identification of FABPs as targets of transport inhibitors undermines the central pharmacological support for the existence of an endocannabinoid transmembrane transporter.
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The anandamide transport inhibitor AM404 activates vanilloid receptors
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TRPV1 in Brain Is Involved in Acetaminophen-Induced Antinociception
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Reduction in endocannabinoid tone is a homeostatic mechanism for specific inhibitory synapses
Kim, J., & Alger, B. E. (2010) · Nature Neuroscience · doi:10.1038/nn.2517 · Cited by 149
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Metadata
- Authors
- Kaczocha, M., Vivieca, S., Sun, J., Glaser, S. T., & Deutsch, D. G.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 287
- Issue
- 5
- Pages
- 3415-3424
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2018780060
- Cited by
- 187
- References
- 8
- FWCI
- 8.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Kaczocha, M., Vivieca, S., Sun, J., Glaser, S. T., & Deutsch, D. G. (2012). Fatty Acid-binding Proteins Transport N-Acylethanolamines to Nuclear Receptors and Are Targets of Endocannabinoid Transport Inhibitors. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m111.304907
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