title: [Endocannabinoids in the central nervous system].
abstract: The major psychoactive component of cannabis derivatives, delta9-THC, activates two G-protein coupled receptors: CB1 and CB2. Soon after the discovery of these receptors, their endogenous ligands were identified: lipid metabolites of arachidonic acid, named endocannabinoids. The two major main and most studied endocannabinoids are anandamide and 2-arachidonyl-glycerol. The CB1 receptor is massively expressed through-out the central nervous system whereas CB2 expression seems restricted to immune cells. Following endocannabinoid binding, CB1 receptors modulate second messenger cascades (inhibition of adenylate cyclase, activation of mitogen-activated protein kinases and of focal-adhesion kinases) as well as ionic conductances (inhibition of voltage-dependent calcium channels, activation of several potassium channels). Endocannabinoids transiently silence synapses by decreasing neurotransmitter release, play major parts in various forms of synaptic plasticity because of their ability to behave as retrograde messengers and activate non-cannabinoid receptors (such as vanilloid receptor type-1), illustrating the complexity of the endocannabinoid system. The diverse cellular targets of endocannabinoids are at the origin of the promising therapeutic potentials of the endocannabinoid system.
authors.affiliation: Laboratoire de neurobiologie pharmacologique, Inserm U.114, Collège de France, 11, place Marcelin-Berthelot, 75005 Paris, France. laurent.venance@college-de-france.fr
authors.forename: Laurent
authors.initials: L
authors.lastname: Venance
authors.forename: Raphael
authors.initials: R
authors.lastname: Maldonado
authors.forename: Olivier
authors.initials: O
authors.lastname: Manzoni
mesh_terms: D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D002186:Cannabinoids / Q000627:therapeutic use; D002490:Central Nervous System / Q000502:physiology*; D063388:Endocannabinoids; D006801:Humans; D018377:Neurotransmitter Agents / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids; D018377:Neurotransmitter Agents