PMID- 21418147
OWN - NLM
STAT- MEDLINE
DCOM- 20120508
LR  - 20211020
IS  - 1748-1716 (Electronic)
IS  - 1748-1708 (Print)
IS  - 1748-1708 (Linking)
VI  - 204
IP  - 2
DP  - 2012 Feb
TI  - The serine hydrolases MAGL, ABHD6 and ABHD12 as guardians of 
      2-arachidonoylglycerol signalling through cannabinoid receptors.
PG  - 267-76
LID - 10.1111/j.1748-1716.2011.02280.x [doi]
AB  - The endocannabinoid 2-arachidonoylglycerol (2-AG) is a lipid mediator involved in 
      various physiological processes. In response to neural activity, 2-AG is 
      synthesized post-synaptically, then activates pre-synaptic cannabinoid CB1 
      receptors (CB1Rs) in a retrograde manner, resulting in transient and long-lasting 
      reduction of neurotransmitter release. The signalling competence of 2-AG is 
      tightly regulated by the balanced action between 'on demand' biosynthesis and 
      degradation. We review recent research on monoacylglycerol lipase (MAGL), ABHD6 
      and ABHD12, three serine hydrolases that together account for approx. 99% of 
      brain 2-AG hydrolase activity. MAGL is responsible for approx. 85% of 2-AG 
      hydrolysis and colocalizes with CB1R in axon terminals. It is therefore ideally 
      positioned to terminate 2-AG-CB1R signalling regardless of the source of this 
      endocannabinoid. Its acute pharmacological inhibition leads to 2-AG accumulation 
      and CB1R-mediated behavioural responses. Chronic MAGL inactivation results in 
      2-AG overload, desensitization of CB1R signalling and behavioural tolerance. 
      ABHD6 accounts for approx. 4% of brain 2-AG hydrolase activity but in neurones it 
      rivals MAGL in efficacy. Neuronal ABHD6 resides post-synaptically, often 
      juxtaposed with CB1Rs, and its acute inhibition leads to activity-dependent 
      accumulation of 2-AG. In cortical slices, selective ABHD6 blockade facilitates 
      CB1R-dependent long-term synaptic depression. ABHD6 is therefore positioned to 
      guard intracellular pools of 2-AG at the site of generation. ABHD12 is highly 
      expressed in microglia and accounts for approx. 9% of total brain 2-AG 
      hydrolysis. Mutations in ABHD12 gene are causally linked to a neurodegenerative 
      disease called PHARC. Whether ABHD12 qualifies as a bona fide member to the 
      endocannabinoid system remains to be established.
CI  - (c) 2011 The Authors. Acta Physiologica (c) 2011 Scandinavian Physiological Society.
FAU - Savinainen, J R
AU  - Savinainen JR
AD  - School of Medicine, Institute of Biomedicine/Physiology, University of Eastern 
      Finland, Kuopio, Finland.
FAU - Saario, S M
AU  - Saario SM
FAU - Laitinen, J T
AU  - Laitinen JT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20110422
PL  - England
TA  - Acta Physiol (Oxf)
JT  - Acta physiologica (Oxford, England)
JID - 101262545
RN  - 0 (Arachidonic Acids)
RN  - 0 (Cannabinoid Receptor Antagonists)
RN  - 0 (Cannabinoid Receptor Modulators)
RN  - 0 (Endocannabinoids)
RN  - 0 (Glycerides)
RN  - 0 (Receptors, Cannabinoid)
RN  - 8D239QDW64 (glyceryl 2-arachidonate)
RN  - EC 3.1.1.23 (ABHD12 protein, human)
RN  - EC 3.1.1.23 (ABHD6 protein, human)
RN  - EC 3.1.1.23 (ABHD6 protein, mouse)
RN  - EC 3.1.1.23 (Abhd12 protein, mouse)
RN  - EC 3.1.1.23 (Monoacylglycerol Lipases)
SB  - IM
EIN - Acta Physiol (Oxf). 2012 Mar;204(3):460
MH  - Animals
MH  - Arachidonic Acids/*metabolism
MH  - Cannabinoid Receptor Antagonists
MH  - Cannabinoid Receptor Modulators/*metabolism
MH  - Endocannabinoids
MH  - Glycerides/*metabolism
MH  - Humans
MH  - Mice
MH  - Microglia/metabolism
MH  - Monoacylglycerol Lipases/*metabolism/physiology
MH  - Neurons/metabolism
MH  - Receptors, Cannabinoid/*metabolism
MH  - Signal Transduction/physiology
MH  - Synaptic Transmission/*physiology
PMC - PMC3320662
EDAT- 2011/03/23 06:00
MHDA- 2012/05/09 06:00
CRDT- 2011/03/23 06:00
PHST- 2011/03/23 06:00 [entrez]
PHST- 2011/03/23 06:00 [pubmed]
PHST- 2012/05/09 06:00 [medline]
AID - 10.1111/j.1748-1716.2011.02280.x [doi]
PST - ppublish
SO  - Acta Physiol (Oxf). 2012 Feb;204(2):267-76. doi: 
      10.1111/j.1748-1716.2011.02280.x. Epub 2011 Apr 22.