title: Phosphatidylinositol-linked novel D(1) dopamine receptor facilitates long-term depression in rat hippocampal CA1 synapses.
abstract: Recent work has demonstrated that a phosphatidylinositol (PI)-linked D(1) dopamine receptor selective agonist, SKF83959, mediates phosphatidylinositol hydrolysis via activation of phospholipase C(beta) in brain. Specific contributions of SKF83959 to synaptic plasticity have not been well elucidated. The aim of the current investigation was to characterize the role of SKF83959 on long-term depression (LTD) in the CA1 region of rat hippocampal slices and to explore the molecular events leading to these changes. The results indicated that SKF83959 stimulation significantly depressed field excitatory postsynaptic potentials (fEPSPs) in a dose-dependent manner and facilitated the induction of LTD by LFS. SKF83959-facilitated LTD required activation of phospholipase C (PLC). NMDA receptors were involved in this response. Calcium chelator, BAPTA-AM prevented SKF83959-facilitated LTD, indicating that cytosolic free calcium concentration ([Ca(2+)](i)) elevation could account for this response. Furthermore, SKF83959-facilitated LTD was significantly depressed in the presence of calcineurin (PP2B) inhibitors cyclosporin A (CsA) and associated with a persistent increase in the expression of calcineurin A. Taken together, these findings demonstrate a novel role for PI-linked D(1) dopamine receptor in the neuromodulation of hippocampal LTD.
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Cai
authors.forename: Zhuang-Li
authors.initials: ZL
authors.lastname: Hu
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Yang
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Chen
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D065095:Calcineurin Inhibitors; D002614:Chelating Agents; D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C080703:SK&F 83959; D016572:Cyclosporine; D019703:Calcineurin; D010738:Type C Phospholipases; D002118:Calcium