Baggelaar_2017_ACS.Chem.Biol_12_852

Reference

Title : Chemical Proteomics Maps Brain Region Specific Activity of Endocannabinoid Hydrolases - Baggelaar_2017_ACS.Chem.Biol_12_852
Author(s) : Baggelaar MP , van Esbroeck AC , van Rooden EJ , Florea BI , Overkleeft HS , Marsicano G , Chaouloff F , van der Stelt M
Ref : ACS Chemical Biology , 12 :852 , 2017
Abstract :

The biosynthetic and catabolic enzymes of the endocannabinoids tightly regulate endocannabinoid-mediated activation of the cannabinoid CB1 receptor. Monitoring the activities of these endocannabinoid hydrolases in different brain regions is, therefore, key to gaining insight into spatiotemporal control of CB1 receptor-mediated physiology. We have employed a comparative chemical proteomics approach to quantitatively map the activity profile of endocannabinoid hydrolases in various mouse brain regions at the same time. To this end, we used two different activity-based probes: fluorophosphonate-biotin (FP-biotin), which quantifies FAAH, ABHD6, and MAG-lipase activity, and MB108, which detects DAGL-alpha, ABHD4, ABHD6, and ABHD12. In total, 32 serine hydrolases were evaluated in the frontal cortex, hippocampus, striatum, and cerebellum. Comparison of endocannabinoid hydrolase activity in the four brain regions revealed that FAAH activity was highest in the hippocampus, and MAGL activity was most pronounced in the frontal cortex, whereas DAGL-alpha was most active in the cerebellum. Comparison of the activity profiles with a global proteomics data set revealed pronounced differences. This could indicate that post-translational modification of the endocannabinoid hydrolases is important to regulate their activity. Next, the effect of genetic deletion of the CB1 receptor was studied. No difference in the enzymatic activity was found in the cerebellum, striatum, frontal cortex, and hippocampus of CB1 receptor knockout animals compared to wild type mice. Our results are in line with previous reports and indicate that the CB1 receptor exerts no regulatory control over the basal production and degradation of endocannabinoids and that genetic deletion of the CB1 receptor does not induce compensatory mechanisms in endocannabinoid hydrolase activity.

PubMedSearch : Baggelaar_2017_ACS.Chem.Biol_12_852
PubMedID: 28106377
Gene_locus related to this paper: human-ABHD4 , human-ABHD6 , human-ABHD12 , human-DAGLA , human-MGLL

Related information

Inhibitor FP-Biotin    FP-TAMRA
Gene_locus FP-Biotin    FP-TAMRA    human-ABHD4    human-ABHD6    human-ABHD12    human-DAGLA    human-MGLL

Citations formats

Baggelaar MP, van Esbroeck AC, van Rooden EJ, Florea BI, Overkleeft HS, Marsicano G, Chaouloff F, van der Stelt M (2017)
Chemical Proteomics Maps Brain Region Specific Activity of Endocannabinoid Hydrolases
ACS Chemical Biology 12 :852

Baggelaar MP, van Esbroeck AC, van Rooden EJ, Florea BI, Overkleeft HS, Marsicano G, Chaouloff F, van der Stelt M (2017)
ACS Chemical Biology 12 :852