title: Endocannabinoids at the synapse a decade after the dies mirabilis (29 March 2001): what we still do not know.
abstract: Endogenous cannabinoids (endocannabinoids, eCBs) are ubiquitous regulators of synaptic transmission in the brain, mediating numerous forms of short- and long-term plasticity, and having strong influences on synapse formation and neurogenesis. Their roles as retrograde messengers that suppress both excitatory and inhibitory transmission are well-established. Yet, despite intensive investigation, many basic aspects of the eCB system are not understood. This brief review highlights recent advances, problems that remain unresolved, and avenues for future exploration. While 2-arachidonoylglycerol (2-AG) is probably the major eCB for intercellular CB1R-dependent signalling, anandamide (AEA) has come to the forefront in several novel contexts, both as a dual endovanilloid/endocannabinoid that regulates synaptic transmission acutely and as the source of a steady eCB tone in hippocampus. Complexities in the cellular processing of 2-AG are receiving renewed attention, as they are increasingly recognized as major determinants of how 2-AG affects cells. Long-standing fundamental issues such as the synthesis pathway for AEA and the molecular mechanism(s) underlying cellular uptake and release of eCBs remain problematical.
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, 655 W. Baltimore Street, Rm 5-025, Baltimore, MD 21201, USA. balgerlab@gmail.com
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Alger
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000502:physiology; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D063388:Endocannabinoids; D005989:Glycerides / Q000502:physiology; D053284:Polyunsaturated Alkamides; D013569:Synapses / Q000502:physiology*
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; C094503:glyceryl 2-arachidonate; C078814:anandamide