Allen J W, Vicini S, Faden A I
Institute for Cognitive and Computational Sciences, Department of Neuroscience, Georgetown University, 3970 Reservoir Road NW, Washington, DC 20007, USA.
Exp Neurol. 2001 Jun;169(2):449-60. doi: 10.1006/exnr.2001.7672.
Both ionotropic and metabotropic glutamate receptors have been implicated in the pathogenesis of neuronal injury. Activation of group I metabotropic glutamate receptors (mGluR) exacerbates neuronal cell death, whereas inhibition is neuroprotective. However, the mechanisms involved remain unknown. Activation of group I mGluR modulates multiple signal transduction pathways including stimulation of phosphoinositide hydrolysis, potentiation of NMDA receptor activity, and release of arachidonic acid. Here we demonstrate that whereas activation of group I mGluR by (S)-3,5-dihydroxyphenylglycine (DHPG) potentiates NMDA-induced currents and intracellular calcium increases in rat cortical neuronal cultures, partial effects of group I mGluR activation or inhibition on neuronal injury induced by oxygen-glucose deprivation remain despite NMDA receptor blockade. DHPG stimulation also increases basal arachidonic acid release from rat neuronal-glial cultures and potentiates injury-induced arachidonic acid release in these cultures. Thus, activation of group I mGluR may exacerbate neuronal injury through multiple mechanisms, which include positive modulation of NMDA receptors and enhanced release of arachidonic acid.
离子型和代谢型谷氨酸受体均与神经元损伤的发病机制有关。I 型代谢型谷氨酸受体（mGluR）的激活会加剧神经元细胞死亡，而抑制则具有神经保护作用。然而，其中涉及的机制仍不清楚。I 型 mGluR 的激活会调节多种信号转导途径，包括刺激磷酸肌醇水解、增强 NMDA 受体活性以及释放花生四烯酸。在此我们证明，虽然在大鼠皮质神经元培养物中，(S)-3,5-二羟基苯甘氨酸（DHPG）激活 I 型 mGluR 会增强 NMDA 诱导的电流并使细胞内钙增加，但尽管 NMDA 受体被阻断，I 型 mGluR 激活或抑制对氧糖剥夺诱导的神经元损伤仍有部分影响。DHPG 刺激还会增加大鼠神经元-胶质细胞培养物中基础花生四烯酸的释放，并增强这些培养物中损伤诱导的花生四烯酸释放。因此，I 型 mGluR 的激活可能通过多种机制加剧神经元损伤，这些机制包括对 NMDA 受体的正向调节和花生四烯酸释放的增强。
