QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, September 15, 2004, 24(37):8068-8074; doi:10.1523/JNEUROSCI.2419-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (21) Citing Articles via Google Scholar Google Scholar Articles by Walter, L. Articles by Stella, N. Search for Related Content PubMed PubMed Citation Articles by Walter, L. Articles by Stella, N. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Compound via MeSH Substance via MeSH

 Previous Article  |  Next Article 

Cellular/Molecular
ATP Induces a Rapid and Pronounced Increase in 2-Arachidonoylglycerol Production by Astrocytes, a Response Limited by Monoacylglycerol Lipase

Lisa Walter,¹ Thien Dinh,³ and Nephi Stella^1,2

Departments of ¹Pharmacology and ²Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington 98195, and ³Department of Pharmacology, University of California, Irvine, California 92697

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 (up to 113-fold of basal 2-AG production at 2.5 min). Our results show that ATP greatly increases, and MGL limits, 2-AG production from astrocytes. We propose that 2-AG may function as a gliotransmitter, with MGL inhibitors potentiating this production and possibly restraining the propagation of harmful neuroinflammation.

Key words: 2-AG; ATP; lipase; cannabinoid; astrocyte; glia

---

Received April 27, 2004; revised June 22, 2004; accepted July 27, 2004.

This article has been cited by other articles:

				M. Kano, T. Ohno-Shosaku, Y. Hashimotodani, M. Uchigashima, and M. Watanabe Endocannabinoid-Mediated Control of Synaptic Transmission Physiol Rev, January 1, 2009; 89(1): 309 - 380. [Abstract] [Full Text] [PDF]

				J. Zhang and C. Chen Endocannabinoid 2-Arachidonoylglycerol Protects Neurons by Limiting COX-2 Elevation J. Biol. Chem., August 15, 2008; 283(33): 22601 - 22611. [Abstract] [Full Text] [PDF]

				Y. Hashimotodani, T. Ohno-Shosaku, and M. Kano Presynaptic Monoacylglycerol Lipase Activity Determines Basal Endocannabinoid Tone and Terminates Retrograde Endocannabinoid Signaling in the Hippocampus J. Neurosci., January 31, 2007; 27(5): 1211 - 1219. [Abstract] [Full Text] [PDF]

				S. Alloisio, R. Aiello, S. Ferroni, and M. Nobile Potentiation of Native and Recombinant P2X7-Mediated Calcium Signaling by Arachidonic Acid in Cultured Cortical Astrocytes and Human Embryonic Kidney 293 Cells Mol. Pharmacol., June 1, 2006; 69(6): 1975 - 1983. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help