Group III metabotropic glutamate receptors as autoreceptors in the cerebellar cortex

Group III metabotropic glutamate receptors as autoreceptors in the cerebellar cortex
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第三组代谢型谷氨酸受体作为小脑皮质中的自身受体

DOI:
10.1038/sj.bjp.0705099
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发表时间:
2003
影响因子:
7.3
通讯作者:
J. Kew
J. Kew
中科院分区:
医学2区
文献类型:
--
作者:
M. Lorez;U. Humbel;Marie;J. Kew

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4a亚型的III组代谢性谷氨酸受体(mGluRs)定位于小脑平行纤维(PF) -浦肯野细胞(PC)突触的突触前活跃区。为了研究III组mGluR自身受体被突触释放谷氨酸激活的必要条件,我们表征了选择性激动剂和拮抗剂对几种不同的PF刺激模式引起的兴奋性突触后电流(EPSCs)的影响。III组mGluR选择性激动剂L - AP4抑制了大鼠脑切片中PF - PC突触的EPSCs, EC50为2.4 μM,最大抑制率为80%。这种L - AP4诱导的抑制被III组mGluR选择性拮抗剂MSOP拮抗,估计平衡解离常数为12.5 μM。配对脉冲或四脉冲PF刺激没有激活突触前III组mGluRs,这表明1 mM MSOP对潜伏期为250-500 ms的相对测试EPSC振幅没有影响。在短破伤风爆发(100 Hz, 60 ms)后,EPSC的增强在MSOP的存在下也没有变化。内源性自身受体激活仅在长时间刺激训练(10 Hz, 4.4 s)中被发现,在1 mM MSOP存在下,EPSC振幅增强了15%。这些观察结果支持III组mGluRs的自身受体功能以及在PF突触的短期突触可塑性中的作用。然而,尽管与谷氨酸释放位点有密切的空间关系,但观察到的低至中等水平的激活表明,还有其他机制调节受体的激活。
Group III metabotropic glutamate receptors (mGluRs) of the subtype 4a are localized within presynaptic active zones of cerebellar parallel fibre (PF)‐Purkinje cell (PC) synapses. In order to investigate the conditions necessary for group III mGluR autoreceptor‐activation by synaptically released glutamate, we characterized the effects of selective agonists and antagonists on excitatory postsynaptic currents (EPSCs) evoked by several distinct PF stimulation patterns. The group III mGluR‐selective agonist L‐AP4 depressed evoked EPSCs at PF‐PC synapses in rat brain slices with an EC50 of 2.4 μM and maximum inhibition of 80%. This L‐AP4‐induced depression was antagonized by the group III mGluR‐selective antagonist MSOP with an estimated equilibrium dissaciation constant of 12.5 μM. Paired‐pulse or four‐pulse PF stimulations did not activate presynaptic group III mGluRs as revealed by the lack of effect of 1 mM MSOP on relative test EPSC amplitudes with latencies of 250–500 ms. The potentiation of a test EPSC evoked 200–500 ms after a short tetanic burst (100 Hz for 60 ms), was also unchanged in the presence of MSOP. Endogenous autoreceptor‐activation was revealed only during prolonged stimulation trains (10 Hz for 4.4 s), where, in the presence of 1 mM MSOP, the EPSC amplitudes were enhanced by 15%. These observations support an autoreceptor function of group III mGluRs and a role in short‐term synaptic plasticity at PF synapses. However, the low to moderate activation levels observed, despite the close spatial relation with glutamate release sites, suggests that additional mechanisms regulate receptor activation.
主动脉压力感受器神经元内吞作用的频率依赖性和 III 组 mGluR 的作用。
DOI: 10.1152/ajpheart.2001.281.1.h387
发表时间: 2001
期刊: American journal of physiology. Heart and circulatory physiology
影响因子: --
作者:
Pamidimukkala,J;Hay,M
通讯作者: Hay,M
代谢型谷氨酸受体对下丘脑大细胞神经元的兴奋性和抑制性突触输入的突触前调节。
DOI: 10.1152/jn.1997.77.2.527
发表时间: 1997
期刊: Journal of neurophysiology.
影响因子: --
作者:
Schrader,LA;Tasker,JG
通讯作者: Tasker,JG
DOI: 10.1126/science.293.5527.98
发表时间: 2001-07-06
期刊: SCIENCE
影响因子: 56.9
作者:
Davare, MA;Avdonin, V;Hell, JW
通讯作者: Hell, JW