Sabelhaus C F, Schröder U H, Breder J, Henrich-Noack P, Reymann K G
Project Group Neuropharmacology, Leibniz Institute for Neurobiology, Brenneckestrabetae 6, D-39118 Magdeburg, Germany.
Br J Pharmacol. 2000 Oct;131(4):655-8. doi: 10.1038/sj.bjp.0703646.
The role of group III metabotropic glutamate receptors (mGluR) in ischaemic neurodegeneration is still unsettled. In order to examine a possible modulatory effect of these receptors on ischaemia-induced damage we tested the novel selective agonist (R, S)-4-phosphonophenylglycine [(R,S)-PPG] after an hypoxic/hypoglycaemic insult in rat hippocampal slices. The recovery of population spike amplitudes in the CA1-region was used as parameter for neuronal viability. (R,S)-PPG significantly improved the recovery of synaptic transmission in the CA1-region even when applied only during the recovery period. The results imply that presynaptic glutamate release after an insult contributes to neurodegeneration. Since agonists of group III mGluR reduce neurotransmitter release - probably via presynaptic autoreceptors - we interpret the results obtained in our in vitro model of hypoxia/hypoglycaemia as support of the hypothesis that group III mGluR agonists might be beneficial drugs against diseases where excitotoxicity is one of the dominant pathological mechanisms.
III组代谢型谷氨酸受体（mGluR）在缺血性神经变性中的作用仍未明确。为了研究这些受体对缺血性损伤可能的调节作用，我们在大鼠海马切片进行缺氧/低血糖损伤后，测试了新型选择性激动剂（R，S）-4-膦酰苯甘氨酸[（R，S）-PPG]。将CA1区群体峰电位幅度的恢复作为神经元活力的参数。即使仅在恢复期应用，（R，S）-PPG也能显著改善CA1区突触传递的恢复。结果表明，损伤后突触前谷氨酸释放会导致神经变性。由于III组mGluR激动剂可能通过突触前自身受体减少神经递质释放，我们将在体外缺氧/低血糖模型中获得的结果解释为支持以下假说：III组mGluR激动剂可能是对抗以兴奋性毒性为主要病理机制之一的疾病的有益药物。
