Journal ArticleDOI
A FAAH-regulated class of N-acyl taurines that activates TRP ion channels.
Alan Saghatelian,Michele K. McKinney,Michael Bandell,and Ardem Patapoutian,Benjamin F. Cravatt +4 more
TLDR
The dramatic elevation in endogenous levels of NATs following acute or chronic inactivation of FAAH, in conjunction with the pharmacological effects of these lipids on TRP channels, suggests the existence of a second major lipid signaling system regulated by FAAH in vivo.Abstract:
Fatty acid amide hydrolase (FAAH) is an integral membrane enzyme that catabolizes several bioactive lipids in vivo. Most of the physiological substrates of FAAH characterized to date belong to the N-acyl ethanolamine (NAE) class of fatty acid amides, including the endocannabinoid anandamide, the anti-inflammatory lipid N-palmitoyl ethanolamine, and the satiating factor N-oleoyl ethanolamine. We recently identified a second structural class of fatty acid amides regulated by FAAH in vivo: the N-acyl taurines (NATs). Global metabolite profiling revealed high concentrations of long chain (≥C20) saturated NATs in the central nervous system (CNS) of FAAH(−/−) mice. Here, we use metabolite profiling to characterize the FAAH−NAT system in peripheral mouse tissues. Livers and kidneys of FAAH(−/−) mice possessed dramatic elevations in NATs, which, in contrast to those detected in the CNS, were enriched in polyunsaturated acyl chains (e.g., C20:4, C22:6). Peripheral NATs rose more than 10-fold within 1 h following ...read more
Citations
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Nociceptors—Noxious Stimulus Detectors
Clifford J. Woolf,Qiufu Ma +1 more
TL;DR: The genesis of nociceptors during development and the intrinsic properties of nock-like neurons that enable them to transduce, conduct, and transmit nocICEptors are highlighted and how their phenotypic plasticity contributes to clinical pain is discussed.
Antidepressant-Like Activity and Modulation of Brain Monoaminergic Transmission by Blockade of Anandamide Hydrolysis
Gabriella Gobbi,Francis Rodriguez Bambico,Regina A. Mangieri,Marco Bortolato,Patrizia Campolongo,Tommaso Cassano,Maria Grazia Morgese,Guy Debonnel,Andrea Duranti,A. Tontini,Giorgio Tarzia,Marco Mor,Viviana Trezza,Steven R. Goldberg,Vincenzo Cuomo,Daniele Piomelli +15 more
TL;DR: Gobi et al. as discussed by the authors showed that URB597, a selective inhibitor of the enzyme fatty acid amide hydrolase, which catalyzes the intracellular hydrolysis of the endocannabinoid anandamide, exerts potent antidepressant-like effects in the mouse tail-suspension test and the rat forced-swim test.
Journal ArticleDOI
Cannabinoids and the expanded endocannabinoid system in neurological disorders.
TL;DR: The biology of cannabinoids, the endocannabinoid system and the expanded endoc cannabinoidoid system are outlined and the involvement in and clinical relevance of these systems and the therapeutic potential of cannabinoids across the spectrum of neurological disease are discussed.
Journal ArticleDOI
Enzymatic Pathways That Regulate Endocannabinoid Signaling in the Nervous System
TL;DR: How delineation of their cognate metabolic enzymes has been translated into the development of chemical and genetic tools to test the role that the endocannabinoid system plays in nervous system signaling and behavior is highlighted.
Journal ArticleDOI
A Second Fatty Acid Amide Hydrolase with Variable Distribution among Placental Mammals
TL;DR: The functional proteomic discovery of a second membrane-associated AS enzyme in humans that displays FAAH activity is reported, suggesting that these proteins may collaborate to control fatty acid amide catabolism in primates.
References
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Modulation of anxiety through blockade of anandamide hydrolysis
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