Functional partnership between mGlu3 and mGlu5 metabotropic glutamate receptors in the central nervous system

NEUROPHARMACOLOGY

卷:128

Article

Di Menna, Luisa¹  Joffe, Max E.²  Iacovelli, Luisa³  Orlando, Rosamaria³  Lindsley, Craig W.²  Mairesse, Jerome⁴  Gressens, Pierre^4,5  Cannella, Milena¹  Caraci, Filippo^6,7  Copani, Agata^6,8  Bruno, Valeria^1,3  Battaglia, Giuseppe¹  Conn, P. Jeffrey²  Nicoletti, Ferdinando^1,3 

[1] IRCCS Neuromed, I-86077 Pozzilli, Italy

[2] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37232 USA

[3] Univ Sapienza Roma, Dept Physiol & Pharmacol, Piazzale Aldo Moro 5, I-00185 Rome, Italy

[4] Univ Paris Diderot, PROTECT, INSERM, Sorbonne Paris Cite, F-1141 Paris, France

[5] St Thomas Hosp, Kings Coll London, Dept Perinatal Hlth & Imaging, Div Imaging Sci & Biomed Engn,Ctr Dev Brain,Kings, London SE1 7EH, England

[6] Univ Catania, Dept Drug Sci, I-95125 Catania, Italy

[7] IRCCS Oasi Maria SS, I-94018 Troina, Italy

[8] CNR, Inst Biostruct & Bioimaging, I-95126 Catania, Italy

关键词: Metabotropic glutamate receptors;    Polyphosphoinositide hydrolysis;    Synaptic plasticity;    Receptor-receptor cross-talk;    Neurodevelopment;    Long-term depression;    Neuronal death;    G-protein beta gamma subunits;   

DOI  :  10.1016/j.neuropharm.2017.10.026

来源: Elsevier

【 摘 要 】

mGlu5 receptors are involved in mechanisms of activity-dependent synaptic plasticity, and are targeted by drugs developed for the treatment of CNS disorders. We report that mGlu3 receptors, which are traditionally linked to the control of neurotransmitter release, support mGlu5 receptor signaling in neurons and largely contribute to the robust mGlu5 receptor-mediated polyphosphoinositide hydrolysis in the early postnatal life. In cortical pyramidal neurons, mGlu3 receptor activation potentiated mGlu5 receptor-mediated somatic Ca2+ mobilization, and mGlu3 receptor-mediated long-term depression in the prefrontal cortex required the endogenous activation of mGlu5 receptors. The interaction between mG1u3 and mGlu5 receptors was also relevant to mechanisms of neuronal toxicity, with mGlu3 receptors shaping the influence of mGlu5 receptors on excitotoxic neuronal death. These findings shed new light into the complex role played by mGlu receptors in physiology and pathology, and suggest reconsideration of some of the current dogmas in the mGlu receptor field. (C) 2017 Elsevier Ltd. All rights reserved.

【 授权许可】

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