scholarly journals UPLC-MS/MS Method for Analysis of Endocannabinoid and Related Lipid Metabolism in Mouse Mucosal Tissue

2021 ◽  
Vol 12 ◽  
Author(s):  
Mark B. Wiley ◽  
Pedro A. Perez ◽  
Donovan A. Argueta ◽  
Bryant Avalos ◽  
Courtney P. Wood ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
The Body ◽  
Mucosal Tissues ◽  
Degradative Enzymes ◽  
Health And Disease ◽  
Amide Hydrolase

The endocannabinoid system is expressed in cells throughout the body and controls a variety of physiological and pathophysiological functions. We describe robust and reproducible UPLC-MS/MS-based methods for analyzing metabolism of the endocannabinoids, 2-arachidonoyl-sn-glycerol and arachidonoyl ethanolamide, and related monoacylglycerols (MAGs) and fatty acid ethanolamides (FAEs), respectively, in mouse mucosal tissues (i.e., intestine and lung). These methods are optimized for analysis of activity of the MAG biosynthetic enzyme, diacylglycerol lipase (DGL), and MAG degradative enzymes, monoacylglycerol lipase (MGL) and alpha/beta hydrolase domain containing-6 (ABHD6). Moreover, we describe a novel UPLC-MS/MS-based method for analyzing activity of the FAE degradative enzyme, fatty acid amide hydrolase (FAAH), that does not require use of radioactive substrates. In addition, we describe in vivo pharmacological methods to inhibit MAG biosynthesis selectively in the mouse small-intestinal epithelium. These methods will be useful for profiling endocannabinoid metabolism in rodent mucosal tissues in health and disease.

scholarly journals Elevated Brain Fatty Acid Amide Hydrolase Induces Depressive-Like Phenotypes in Rodent Models: A Review

2021 ◽  
Vol 22 (3) ◽  
pp. 1047
Author(s):  
Dorsa Rafiei ◽  
Nathan J. Kolla
Keyword(s):  
Depressive Symptoms ◽  
Fatty Acid ◽  
Animal Models ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Animal Models Of Depression ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Altered activity of fatty acid amide hydrolase (FAAH), an enzyme of the endocannabinoid system, has been implicated in several neuropsychiatric disorders, including major depressive disorder (MDD). It is speculated that increased brain FAAH expression is correlated with increased depressive symptoms. The aim of this scoping review was to establish the role of FAAH expression in animal models of depression to determine the translational potential of targeting FAAH in clinical studies. A literature search employing multiple databases was performed; all original articles that assessed FAAH expression in animal models of depression were considered. Of the 216 articles that were screened for eligibility, 24 articles met inclusion criteria and were included in this review. Three key findings emerged: (1) FAAH expression is significantly increased in depressive-like phenotypes; (2) genetic knockout or pharmacological inhibition of FAAH effectively reduces depressive-like behavior, with a dose-dependent effect; and (3) differences in FAAH expression in depressive-like phenotypes were largely localized to animal prefrontal cortex, hippocampus and striatum. We conclude, based on the animal literature, that a positive relationship can be established between brain FAAH level and expression of depressive symptoms. In summary, we suggest that FAAH is a tractable target for developing novel pharmacotherapies for MDD.

scholarly journals A Second Generation of Carbamate-Based Fatty Acid Amide Hydrolase Inhibitors with Improved Activity in vivo

ChemMedChem ◽  
2009 ◽  
Vol 4 (9) ◽  
pp. 1505-1513 ◽  
Author(s):  
Jason R. Clapper ◽  
Federica Vacondio ◽  
Alvin R. King ◽  
Andrea Duranti ◽  
Andrea Tontini ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Second Generation ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Fatty Acid Amide Hydrolase Inhibitors from Virtual Screening of the Endocannabinoid System

2006 ◽  
Vol 49 (15) ◽  
pp. 4650-4656 ◽  
Author(s):  
Susanna M. Saario ◽  
Antti Poso ◽  
Risto O. Juvonen ◽  
Tomi Järvinen ◽  
Outi M. H. Salo-Ahen
Keyword(s):  
Fatty Acid ◽  
Virtual Screening ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

scholarly journals Equipotent Inhibition of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase – Dual Targets of the Endocannabinoid System to Protect against Seizure Pathology

2012 ◽  
Vol 9 (4) ◽  
pp. 801-813 ◽  
Author(s):  
Vinogran Naidoo ◽  
David A. Karanian ◽  
Subramanian K. Vadivel ◽  
Johnathan R. Locklear ◽  
JodiAnne T. Wood ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Monoacylglycerol Lipase ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Endocannabinoid System: Overview and Therapeutic Relevance

2021 ◽  
Author(s):  
Alex Mabou Tagne
Keyword(s):  
Fatty Acid ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Receptor Subtypes ◽  
Monoacylglycerol Lipase ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

The endocannabinoid system (ECS) modulates a variety of physiological processes, attracting considerable attention as a potential target for therapeutic intervention. This complex system is activated by the lipid-derived mediators anandamide and 2-arachidonoyl-sn-glycerol (2-AG), which mainly engage the cannabinoid receptor subtypes 1 (CB1) and 2 (CB2). The biological actions of anandamide and 2-AG are terminated by internalization and intracellular enzymatic hydrolysis catalyzed primarily by the serine hydrolases fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL), respectively. Here, we provide an overview of ECS and discuss the implications for advancing pharmacological tools that interfere with such a system as next-generation therapeutics. This review contains 4 figures, 3 tables and 41 references Keywords: Endocannabinoid; anandamide; 2-Arachidonoyl-sn-glycerol; fatty acid amide hydrolase; monoacylglycerol lipase; cannabinoid receptors; N-acylethanolamine acid amidase; Δ9-tetrahydrocannabinol.

Enol Carbamates as Inhibitors of Fatty Acid Amide Hydrolase (FAAH) Endowed with High Selectivity for FAAH over the Other Targets of the Endocannabinoid System

ChemMedChem ◽  
2010 ◽  
Vol 5 (3) ◽  
pp. 357-360 ◽  
Author(s):  
Sonia Gattinoni ◽  
Chiara De Simone ◽  
Sabrina Dallavalle ◽  
Filomena Fezza ◽  
Raffaella Nannei ◽  
...  
Keyword(s):  
Fatty Acid ◽  
High Selectivity ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
The Other ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

scholarly journals Blocking of Fatty Acid Amide Hydrolase Activity with PF-04457845 in Human Brain: A Positron Emission Tomography Study with the Novel Radioligand [11C]CURB

2015 ◽  
Vol 35 (11) ◽  
pp. 1827-1835 ◽  
Author(s):  
Isabelle Boileau ◽  
Pablo M Rusjan ◽  
Belinda Williams ◽  
Esmaeil Mansouri ◽  
Romina Mizrahi ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Fatty Acid ◽  
Human Brain ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Emission Tomography ◽  
Positron Emission ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Positron emission tomography with [11C]CURB was recently developed to quantify fatty acid amide hydrolase (FAAH), the enzyme responsible for hydrolyzing the endocannabinoid anandamide. This study investigated the test–retest reliability of [11C]CURB as well as its in vivo specificity and the validity of the kinetic model by using the highly specific FAAH inhibitor, PF-04457845. Five healthy volunteers completed test–retest [11C]CURB scans 1 to 2 months apart and six subjects completed baseline and blocking scans on the same day after PF-04457845 (p.o.) administration (1, 4, or 20 mg; n = 2 each). The composite parameter γ k3 (an index of FAAH activity, γ = K1/ k2) was estimated using an irreversible two-tissue compartment model with plasma input function. There were no clinically observable responses to oral PF-04457845 or [11C]CURB injection. Oral administration of PF-04457845 reduced [11C]CURB binding to a homogeneous level at all three doses, with γ k3 values decreased by ≥91%. Excellent reproducibility and good reliability (test–retest variability = 9%; intraclass correlation coefficient = 0.79) were observed across all regions of interest investigated. Our findings suggest that γ k3/[11C]CURB is a reliable, highly sensitive, and selective tool to measure FAAH activity in human brain in vivo. Moreover, PF-04457845 is a highly potent FAAH inhibitor (>95% inhibition at 1 mg) in living human brain.

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