Enhancement of NMDA responses by group I metabotropic glutamate receptor activation in striatal neurones
Enhancement of NMDA responses by group I metabotropic glutamate receptor activation in striatal neurones
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DOI：
10.1038/sj.bjp.0700999
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发表时间：
1997-03-01
影响因子：
7.3
通讯作者：
Bernardi, G
中科院分区：
文献类型：
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作者：
Pisani, A;Calabresi, P;Bernardi, G
在纹状体切片中，利用电流和电压钳模式下的细胞内记录，研究了n -甲基- d -天冬氨酸（NMDA）和代谢性谷氨酸受体（mGluRs）之间的相互作用浸泡（50 μ M）或局部应用NMDA诱导瞬态膜去极化，而在电压钳形模式下，NMDA （50 μ M）引起瞬态内向电流。在非选择性mGluR激动剂1S， 3r -氨基环戊烷-1,3-二羧酸（1S,3R-ACPD, 10 μ M）中，NMDA反应在电流（197+/-15%对照）和电压钳实验（200+/-18%对照）中均可逆增强1组mGluR激动剂(RS)-3,5-二羟基苯基甘氨酸（3,5- dhpg, 10-300 μ M）的盆浴应用导致nmda诱导的膜去极化呈剂量依赖性增强（高达对照的400+/-33%）。这种增强作用可以通过(RS)- α -甲基-4-羧基苯基甘氨酸（RS- α - mcpg, 300 μ M）预孵育来阻止，或者在3,5- dhpg冲洗后立即应用来阻断II组mGluRs的激动剂（2S,1' s,2' s）2-（2'-羧基环丙基）甘氨酸（L-CCG I，最多100 μ M）和(2S,1' r,2' r,3'R)-2-（2,3-二羧基环丙基）-甘氨酸（DCG-IV, 1 μ M）都没有引起NMDA反应的任何变化。同样，III组mGluRs的激动剂l -丝氨酸-磷酸（L-SOP, 30 μ M）也不影响nmda诱导的去极化激活蛋白激酶C （PKC）的phorpol -12,13-diacetate （PDAc, 1 μ M）可以模拟NMDA反应的增强。用staurosporine （100 nM）或calphostin C （1 μ M）预孵育可以阻止3,5- dhpg介导的nmda诱导的去极化增强，PKC.6拮抗剂对α -氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体激活的电生理反应不受3类mglur激动剂的影响目前的数据表明，I组mGluRs可能通过激活PKC对NMDA反应发挥积极的调节作用。纹状体中的这种功能相互作用在理解生理和病理事件（如突触可塑性和神经元死亡）中显得至关重要。
1 The interactions between N-methyl-D-aspartate (NMDA) and metabotropic glutamate receptors (mGluRs) were investigated in striatal slices, by utilizing intracellular recordings, both in current- and voltage-clamp mode.2 Bath-application (50 mu M) or focal application of NMDA induced a transient membrane depolarization, while in the voltage-clamp mode, NMDA (50 mu M) caused a transient inward current. Following bath-application of the non-selective mGluR agonist 1S,3R-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD, 10 mu M), NMDA responses were reversibly potentiated both in current (197+/-15% of control) and voltage-clamp experiments (200+/-18% of control).3 Bath-application of the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (3,5-DHPG, 10-300 mu M) resulted in a dose-dependent potentiation of NMDA-induced membrane depolarization (up to 400+/-33% of control). This potentiation was either prevented by preincubation with (RS)-alpha-methyl-4-carboxyphenylglycine (RS-alpha-MCPG, 300 mu M), or blocked when applied immediately after 3,5-DHPG wash-out.4 Neither (2S,1'S,2'S)2-(2'-carboxycyciopropyl)glycine (L-CCG I, up to 100 mu M) nor (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)-glycine (DCG-IV, 1 mu M), agonists for group II mGluRs caused any change in NMDA responses. Likewise, L-serine-O-phosphate (L-SOP, 30 mu M), agonist for group III mGluRs, did not affect the NMDA-induced depolarization.5 The enhancement of the NMDA responses was mimicked by phorbol-12,13-diacetate (PDAc, 1 mu M) which activates protein kinase C (PKC). The 3,5-DHPG-mediated potentiation of the NMDA-induced depolarization was prevented by preincubation with staurosporine (100 nM) or calphostin C (1 mu M), antagonists of PKC.6 Electrophysiological responses to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor activation were not affected by agonists for the three-classes of mGluRs.7 The present data suggest that group I mGluRs exert a positive modulatory action on NMDA responses, probably through activation of PKC. This functional interaction in the striatum appears of crucial importance in the understanding of physiological and pathological events, such as synaptic plasticity and neuronal death, respectively.