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

This Article Full Text Full Text (PDF) All Versions of this Article: mol.105.013961v1 68/5/1196    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal 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 Google Scholar Google Scholar Articles by Jung, K.-M. Articles by Piomelli, D. Search for Related Content PubMed PubMed Citation Articles by Jung, K.-M. Articles by Piomelli, D.

Stimulation of Endocannabinoid Formation in Brain Slice Cultures through Activation of Group I Metabotropic Glutamate Receptors

Department of Psychiatry and Human Behavior (K.-M.J., C.S., J.K.), Department of Pharmacology (R.M., D.F., D.P.), and Center for Drug Discovery (K.-M.J., R.M., C.S., D.P.), University of California, Irvine, California; and Department of Anesthesiology, University of Washington, Seattle, Washington (M.W., K.M.)

Activation of group I metabotropic glutamate (mGlu) receptors drives the endocannabinoid system to cause both short- and long-term changes of synaptic strength in the striatum, hippocampus, and other brain areas. Although there is strong electrophysiological evidence for a role of endocannabinoid release in mGlu receptor-dependent plasticity, the identity of the endocannabinoid transmitter mediating this phenomenon remains undefined. In this study, we show that activation of group I mGlu receptors triggers the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG), but not anandamide, in primary cultures of corticostriatal and hippocampal slices prepared from early postnatal rat brain. Pharmacological studies suggest that 2-AG biosynthesis is initiated by activation of mGlu5 receptors, is catalyzed by phospholipase C (PLC) and 1,2-diacylglycerol lipase (DGL) activities, and is dependent on intracellular Ca²⁺ ions. Realtime polymerase chain reaction and immunostaining analyses indicate that DGL- is the predominant DGL isoform expressed in corticostriatal and hippocampal slices and that this enzyme is highly expressed in striatal neurons, where it is colocalized with PLC-1. The results suggest that 2-AG is a primary endocannabinoid mediator of mGlu receptor-dependent neuronal plasticity.

Address correspondence to: Dr. Daniele Piomelli, Department of Pharmacology, 3101 Gillespie NRF, University of California, Irvine, CA 92697-4625. E-mail: piomelli{at}uci.edu

This article has been cited by other articles:

				D. A. Edwards, L. Zhang, and B. E. Alger Metaplastic control of the endocannabinoid system at inhibitory synapses in hippocampus PNAS, June 10, 2008; 105(23): 8142 - 8147. [Abstract] [Full Text] [PDF]

				B. Pan, C. J. Hillard, and Q.-s. Liu Endocannabinoid Signaling Mediates Cocaine-Induced Inhibitory Synaptic Plasticity in Midbrain Dopamine Neurons J. Neurosci., February 6, 2008; 28(6): 1385 - 1397. [Abstract] [Full Text] [PDF]

				G. M. Drew, V. A. Mitchell, and C. W. Vaughan Glutamate Spillover Modulates GABAergic Synaptic Transmission in the Rat Midbrain Periaqueductal Grey via Metabotropic Glutamate Receptors and Endocannabinoid Signaling J. Neurosci., January 23, 2008; 28(4): 808 - 815. [Abstract] [Full Text] [PDF]

				A.H. Taylor, C. Ang, S.C. Bell, and J.C. Konje The role of the endocannabinoid system in gametogenesis, implantation and early pregnancy Hum. Reprod. Update, September 1, 2007; 13(5): 501 - 513. [Abstract] [Full Text] [PDF]

				K.-M. Jung, G. Astarita, C. Zhu, M. Wallace, K. Mackie, and D. Piomelli A Key Role for Diacylglycerol Lipase-{alpha} in Metabotropic Glutamate Receptor-Dependent Endocannabinoid Mobilization Mol. Pharmacol., September 1, 2007; 72(3): 612 - 621. [Abstract] [Full Text] [PDF]

				S. Oka, S. Arai, K. Waku, A. Tokumura, and T. Sugiura Depolarization-induced Rapid Generation of 2-Arachidonoylglycerol, an Endogenous Cannabinoid Receptor Ligand, in Rat Brain Synaptosomes J. Biochem., May 1, 2007; 141(5): 687 - 697. [Abstract] [Full Text] [PDF]

				Y. Hashimotodani, T. Ohno-Shosaku, and M. Kano Endocannabinoids and Synaptic Function in the CNS Neuroscientist, April 1, 2007; 13(2): 127 - 137. [Abstract] [PDF]

				B. Szabo, M. J. Urbanski, T. Bisogno, V. D. Marzo, A. Mendiguren, W. U. Baer, and I. Freiman Depolarization-induced retrograde synaptic inhibition in the mouse cerebellar cortex is mediated by 2-arachidonoylglycerol J. Physiol., November 15, 2006; 577(1): 263 - 280. [Abstract] [Full Text] [PDF]

				I. Katona, G. M. Urban, M. Wallace, C. Ledent, K.-M. Jung, D. Piomelli, K. Mackie, and T. F. Freund Molecular Composition of the Endocannabinoid System at Glutamatergic Synapses J. Neurosci., May 24, 2006; 26(21): 5628 - 5637. [Abstract] [Full Text] [PDF]

				H. H. Yin and D. M. Lovinger Frequency-specific and D2 receptor-mediated inhibition of glutamate release by retrograde endocannabinoid signaling PNAS, May 23, 2006; 103(21): 8251 - 8256. [Abstract] [Full Text] [PDF]

				M. Isokawa and B. E. Alger Ryanodine Receptor Regulates Endogenous Cannabinoid Mobilization in the Hippocampus J Neurophysiol, May 1, 2006; 95(5): 3001 - 3011. [Abstract] [Full Text] [PDF]