title: Endocannabinoids generated by Ca2+ or by metabotropic glutamate receptors appear to arise from different pools of diacylglycerol lipase.
abstract: The identity and subcellular sources of endocannabinoids (eCBs) will shape their ability to affect synaptic transmission and, ultimately, behavior. Recent discoveries support the conclusion that 2-arachidonoyl glycerol, 2-AG, is the major signaling eCB, however, some important issues remain open. 2-AG can be synthesized by a mechanism that is strictly Ca(2+)-dependent, and another that is initiated by G-protein coupled receptors (GPCRs) and facilitated by Ca(2+). An important question is whether or not the 2-AG in these cases is synthesized by the same pool of diacylglycerol lipase alpha (DAGLα). Using whole-cell voltage-clamp techniques in CA1 pyramidal cells in acute in vitro rat hippocampal slices, we investigated two mechanistically distinct eCB-mediated responses to address this issue. We now report that pharmacological inhibitors of DGLα have quantitatively different effects on eCB-mediated responses triggered by different stimuli, suggesting that functional, and perhaps physical, distinctions among pools of DAGLα exist.
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Longhua
authors.initials: L
authors.lastname: Zhang
authors.forename: Meina
authors.initials: M
authors.lastname: Wang
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bisogno
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Alger
mesh_terms: D000818:Animals; D001095:Arachidonic Acids; D056547:CA1 Region, Hippocampal / Q000166:cytology; D002118:Calcium / Q000378:metabolism*; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D063388:Endocannabinoids; D005989:Glycerides; D008071:Lipoprotein Lipase / Q000378:metabolism* / Q000502:physiology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D018094:Receptors, Metabotropic Glutamate; C094503:glyceryl 2-arachidonate; D008071:Lipoprotein Lipase; D002118:Calcium