TY -的T1 -摩根富林明Metabotropic谷氨酸受体-神经学乔-神经病学SP - 964 LP 首页- 968——10.1212/01. wnl.0000306315.03021.2a六世- 70 - 12盟爱德华多e Benarroch Y1 - 2008/03/18 UR - //www.ez-admanager.com/content/70/12/964.abstract N2 - AC =腺苷酸环化酶;DAG =甘油二酯;FMRP =脆性X智力缺陷蛋白;FXS =脆性X综合征;G =鸟嘌呤;GPCR =鸟嘌呤核苷酸结合蛋白的受体;GPe =苍白球外部的部分;GPi =苍白球的内部部分;IP3 =三磷酸肌醇;有限公司=长期抑郁; LTP=long-term potentiation; mGluR=metabotropic glutamate receptor; PKC=protein kinase C; PLC=phospholipase C; SNc=substantia nigra pars compacta; SNr=substantia nigra pars reticulata; STN=subthalamic nucleus; SWD=spike-and-wave discharges. Glutamate is the primary excitatory neurotransmitter in the CNS and acts via two main classes of receptors: ionotropic and metabotropic. Whereas ionotropic receptors are responsible for fast excitatory synaptic transmission, metabotropic glutamate receptors (mGluRs) have an important role in synaptic modulation throughout the CNS. Different subtypes of mGluRs regulate neuronal excitability, synaptic plasticity, neurotransmitter release, and glial functions, which are important for brain development and mechanisms of learning, injury, and neuroprotection.1–8 Not surprisingly, mGluRs have been implicated in the pathophysiology of several neurologic and psychiatric disorders, including hypoxic injury, epilepsy, Parkinson disease, Alzheimer disease, pain, anxiety, schizophrenia, and drug addiction. The development of selective non-competitive allosteric modulators of different subtypes of mGluRs allows elucidating the physiologic role of these receptors and their potential as therapeutic targets in neurologic disorders.9–11 This brief review focuses on the synaptic effects of mGluRs in some representative circuits and the potential clinical and therapeutic implications. Several publications provide a comprehensive coverage of these and related topics.1,3,5,8–16 The metabotropic receptors (mGluRs) are guanine nucleotide binding (G)-protein coupled receptors (GPCRs) that consist of dimers of subunits with seven transmembrane domains.1,2 There are eight subtypes of mGluRs that are classified, according to their structure, transduction mechanisms, and pharmacology into group I (mGluR1 and mGluR5), group II (mGlu2 and mGlu3), and group III (mGluR4, mGluR6, mGluR7, and mGluR8) receptors1–3 (table 1). Some of these receptors include several isoforms. View this table:In this windowIn a new window Table 1 Overview of metabotropic glutamate receptors Group I receptors (mGluR1 and mGluR5) are positively coupled to phospholipase C, and trigger calcium (Ca2+) release from the endoplasmic reticulum and activation of protein kinase C. These receptors also potentiate l-type Ca2+ channels and inhibit K+ channels. Type I mGluRs may also act independently of G proteins to activate transducing cascades that trigger phosphorylation of … ER -