Effect of agmatine on heteromeric N-methyl-D-aspartate receptor channels
Effect of agmatine on heteromeric N-methyl-D-aspartate receptor channels
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DOI：
10.1016/j.neures.2005.05.002
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发表时间：
2005-08-01
影响因子：
2.9
通讯作者：
Baba, H
中科院分区：
文献类型：
--
作者：
Askalany, AR;Yamakura, T;Baba, H
已知内源性多胺如精胺对重组N-甲基-D-天冬氨酸（NMDA）受体通道具有四种不同的作用：电压依赖性抑制、甘氨酸依赖性刺激、甘氨酸非依赖性刺激和对激动剂（L-谷氨酸）的亲和力降低。这些作用高度依赖于重组NMDA受体通道的组成F亚基（R1-R4）。据报道，胍丁胺抑制培养的海马神经元中的天然NMDA受体通道。本研究采用双电极电压钳方法研究胍丁胺对非洲爪蟾卵母细胞表达的N-甲基-D-天冬氨酸（NMDA）受体通道的影响。胍丁胺以相似的敏感性抑制四种β/zeta（β 1/zeta 1、β 2/zeta 1、β 4/zeta 1和β 4/zeta 1）通道（在-70 mV时IC 50值约为300 μ M）。这种效应取决于膜电位，并且在超极化膜电位下更加明显（电压依赖性抑制）。胍丁胺没有表现出其他刺激性（甘氨酸依赖性和非依赖性作用）或抑制性（降低对L-谷氨酸的亲和力）作用。这些特性与充分表征的NMDA受体通道阻滞剂（如苯环利定和氯胺酮）的药理学特征相似。因此，关于对NMDA受体通道的作用，胍丁胺不像其他内源性多胺，而是作为通道阻断剂。(c)2005年Elsevier爱尔兰有限公司和日本神经科学学会。All rights reserved.
Endogenous polyamines like spermine are known to have four distinct effects on recombinant N-methyl-D-aspartate (NMDA) receptor channels: voltage-dependent inhibition, glycine-dependent Stimulation, glycine-independent stimulation and decreased affinity to the agonist (L-glutamate). These effects are highly dependent on the constituting F subunits (epsilon 1-r4) of the recombinant NMDA receptor channels. Agmatine reportedly inhibits native NMDA receptor channels in cultured hippocampal neurons. In the present investigation, the effects of agmatine on the epsilon/zeta heteromeric NMDA receptor channels expressed in Xenopus laevis oocytes were examined using the two-electrode voltage clamp method. Agmatine inhibited the four epsilon/zeta (epsilon 1/zeta 1, epsilon 2/zeta 1, epsilon 4/zeta 1 and epsilon 4/zeta 1) channels with similar sensitivity (an IC50 value of about 300 mu M at -70 mV). This effect was dependent on the membrane potential and was more pronounced at hyperpolarized membrane potentials (vottage-dependent inhibition). Agmatine did not exhibit other stimulatory (glycine-dependent and -independent effects) or inhibitory (decreased affinity to L-glutamate) effects. These properties are similar to the pharmacological profile of well-characterized NMDA receptor channel blockers like phencyclidine and ketamine. Thus, regarding the effects on the NMDA receptor channels, agmatine is not like other endogenous polyamines rather it acts as a channel blocker. (c) 2005 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.