Metabotropic glutamate receptors
Metabotropic glutamate receptors
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DOI：
10.1007/s00726-006-0315-0
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发表时间：
2007-01
期刊：
影响因子：
3.5
通讯作者：
Andrzej Pilc;K. Ossowska
中科院分区：
文献类型：
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作者：
Andrzej Pilc;K. Ossowska
据估计，CA。脑中50%的神经元可以利用谷氨酸作为神经递质（McGeer等人，1987年）。谷氨酸，中枢神经系统（CNS）中的主要兴奋性氨基酸，通过刺激离子型（iGlu）和代谢型（mGlu）受体起作用（Monaghan等人，1989）并且似乎在生理学和病理生理学中起主要作用（参见Kretschmer等人，2002年）。有资料表明，离子型谷氨酸神经传递的改变可能参与多种神经精神疾病的发生（Wroblewski和Danysz，1989）。越来越多的证据表明，谷氨酸受体在抗抑郁药的作用机制中起着至关重要的作用。（综述参见Palucha和Pilc，2005）、抗精神病药（Moghlovan和亚当斯，1998; Moghlovan，2004）和抗帕金森病药（综述参见Ossowska，1994）。离子型谷氨酸受体（iGlu）拮抗剂（主要是NMDA受体拮抗剂）可用于多种CNS病症的巨大希望受到以下事实的阻碍，即这些化合物在临床前研究中产生明显的不良反应，例如拟精神病作用、记忆障碍和共济失调（Danysz等人，1996年）。iGlu受体拮抗剂产生的副作用问题的可能解决方案之一是通过使用充当代谢型谷氨酸（mGlu）受体的配体的物质来调节谷氨酸能系统的功能。代谢型谷氨酸受体是一类新的G蛋白偶联受体C家族的成员
It has been estimated that ca. 50% of neurons in the brain may utilize glutamate as a neurotransmitter (McGeer et al., 1987). Glutamate, the major excitatory amino acid in the central nervous system (CNS) acts by stimulating ionotropic (iGlu) and metabotropic (mGlu) receptors (Monaghan et al., 1989) and seems to play a major role in both physiology and pathophysiology (see Kretschmer et al., 2002). Some data show that changes in ionotropic glutamate neurotransmission may be involved in a variety of neuropsychiatric disorders (Wroblewski and Danysz, 1989).Converging lines of evidence indicate a crucial involvement of glutamate receptors in the mechanism of action of antidepressant (for review see Palucha and Pilc, 2005), antipsychotic (Moghaddam and Adams, 1998; Moghaddam, 2004) and antiparkinsonian drugs (for review see Ossowska, 1994). The great hope that ionotropic glutamate receptor (iGlu) antagonists, mainly NMDA receptor antagonists, could be used for a variety of CNS disorders was hampered by the fact that these compounds produce pronounced adverse reactions, such as psychotomimetic effects, memory impairment and ataxia in preclinical studies (Danysz et al., 1996). One of the possible solutions to the problem of adverse effects produced by iGlu receptor antagonists is to modulate the function of the glutamatergic system by using substances acting as ligands of metabotropic glutamate (mGlu) receptors. Metabotropic glutamate receptors are members of a novel class of the C family of G protein-coupled receptors