ATP induces a rapid and pronounced increase in 2-arachidonoylglycerol production by astrocytes, a response limited by monoacylglycerol lipase

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Lisa WalterNephi Stella

Abstract

The cytoplasm of neural cells contain millimolar amounts of ATP, which flood the extracellular space after injury, activating purinergic receptors expressed by glial cells and increasing gliotransmitter production. These gliotransmitters, which are thought to orchestrate neuroinflammation, remain widely uncharacterized. Recently, we showed that microglial cells produce 2-arachidonoylglycerol (2-AG), an endocannabinoid known to prevent the propagation of harmful neuroinflammation, and that ATP increases this production by threefold at 2.5 min (Witting et al., 2004). Here we show that ATP increases 2-AG production from mouse astrocytes in culture, a response that is more rapid (i.e., significant within 10 sec) and pronounced (i.e., 60-fold increase at 2.5 min) than any stimulus-induced increase in endocannabinoid production reported thus far. Increased 2-AG production from astrocytes requires millimolar amounts of ATP, activation of purinergic P2X7 receptors, sustained rise in intracellular calcium, and diacylglycerol lipase activity. Furthermore, we show that astrocytes express monoacylglycerol lipase (MGL), the main hydrolyzing enzyme of 2-AG, the pharmacological inhibition of which potentiates the ATP-induced 2-AG production (...Continue Reading

Citations

Mar 14, 2009·Molecular Neurobiology·Alexei VerkhratskyGeoffrey Burnstock
Apr 24, 2008·Chemical Reviews·Kay AhnBenjamin F Cravatt
Jun 22, 2011·Proceedings of the National Academy of Sciences of the United States of America·Onder AlbayramAndras Bilkei-Gorzo
Nov 18, 2010·The Journal of Biological Chemistry·Cécile DelarasseJean M Kanellopoulos
Jun 7, 2008·The Journal of Biological Chemistry·Jian Zhang, Chu Chen
Oct 31, 2012·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Andras Bilkei-Gorzo
May 6, 2011·Molecular Neurodegeneration·Zsuzsanna HracskóBeáta Sperlágh
Jun 14, 2012·PloS One·Yoshifumi IwamaruHiroshi Kitani
Dec 7, 2013·PloS One·Peter M ZygmuntEdward D Högestätt
Nov 15, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Shi DiJeffrey G Tasker
Feb 16, 2011·Seminars in Cell & Developmental Biology·Ulyana LaloYuri Pankratov
Feb 16, 2010·Immunobiology·Lucie Jean-GillesCris S Constantinescu
Mar 3, 2009·Journal of Neurochemistry·Cécile DelarasseJean M Kanellopoulos
May 21, 2009·The European Journal of Neuroscience·Rita NyilasIstván Katona
May 5, 2006·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Nicholas BardenBertram Müller-Myhsok
Jan 3, 2013·Fundamental & Clinical Pharmacology·Panagiotis ZogopoulosStamatios E Theocharis
Jan 1, 2012·Wiley Interdisciplinary Reviews. Membrane Transport and Signaling·Alexei VerkhratskyMaiken Nedergaard
Jul 28, 2015·Cell Reports·Andreu ViaderBenjamin F Cravatt
Jul 2, 2010·British Journal of Pharmacology·Matthew W Buczynski, Loren H Parsons
Nov 21, 2015·Nature Reviews. Neuroscience·Beat LutzCecilia J Hillard
Sep 10, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Niina AaltonenJarmo T Laitinen
Jan 13, 2009·Advanced Drug Delivery Reviews·Csilla HegedusBalázs Sarkadi
Feb 3, 2018·European Archives of Psychiatry and Clinical Neuroscience·Valéria de Almeida, Daniel Martins-de-Souza
Jul 31, 2007·Human Mutation·Tine Venken, Jurgen Del-Favero
Jan 8, 2009·Physiological Reviews·Masanobu KanoMasahiko Watanabe
Jan 31, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Zoltán BenyóPál Pacher
Jan 20, 2018·Physiological Reviews·Alexei Verkhratsky, Maiken Nedergaard

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