title: Oxytocin Stimulates Extracellular Ca2+ Influx Through TRPV2 Channels in Hypothalamic Neurons to Exert Its Anxiolytic Effects.
abstract: There is growing interest in anxiolytic and pro-social effects of the neuropeptide oxytocin (OXT), but the underlying intraneuronal mechanisms are largely unknown. Here we examined OXT-mediated anxiolysis in the hypothalamic paraventricular nucleus (PVN) of rats and effects of OXT administration on signaling events in hypothalamic primary and immortalized cells. In vivo, the application of SKF96365 prevented the anxiolytic activity of OXT in the PVN, suggesting that changes in intracellular Ca(2+) mediate the acute OXT behavioral effects. In vitro, mainly in the neurons with autonomous Ca(2+) oscillations, OXT increased intracellular Ca(2+) concentration and oscillation amplitude. Pharmacological intervention revealed OXT-dependent changes in Ca(2+) signaling that required activation of transient receptor potential vanilloid type-2 channel (TRPV2), mediated by phosphoinositide 3-kinase. TRPV2 induced the activation of the anxiolytic mitogen-activated protein kinase kinase (MEK1/2). In situ, immunohistochemistry revealed co-localization of TRPV2 and OXT in the PVN. Thus, functional and pharmacological analyses identified TRPV2 as a mediator of anxiolytic effects of OXT, conveying the OXT signal to MEK1/2 via modulation of intracellular Ca(2+).
authors.affiliation: Department of Behavioural and Molecular Neurobiology, Institute of Zoology, University of Regensburg, Regensburg, Germany.
authors.forename: Erwin H
authors.initials: EH
authors.lastname: van den Burg
authors.affiliation: Department of Experimental Ophthalmology, Eye Hospital, University Medical Center Regensburg, Regensburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Stindl
authors.affiliation: Department of Behavioural and Molecular Neurobiology, Institute of Zoology, University of Regensburg, Regensburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Grund
authors.affiliation: Department of Behavioural and Molecular Neurobiology, Institute of Zoology, University of Regensburg, Regensburg, Germany.
authors.forename: Inga D
authors.initials: ID
authors.lastname: Neumann
authors.affiliation: Department of Experimental Ophthalmology, Eye Hospital, University Medical Center Regensburg, Regensburg, Germany.|Experimental Ophthalmology, Department of Ophthalmology, Charite University Medicine Berlin, Berlin, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Strauss
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002413:Cations, Divalent / Q000378:metabolism; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D005110:Extracellular Space / Q000187:drug effects* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010121:Oxytocin / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D014151:Anti-Anxiety Agents; D002121:Calcium Channel Blockers; D002413:Cations, Divalent; D007093:Imidazoles; D018045:Receptors, Oxytocin; D050916:TRPV Cation Channels; C476722:Trpv2 protein, rat; D010121:Oxytocin; D019869:Phosphatidylinositol 3-Kinases; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium