Stimulatory and inhibitory properties of aminoglycoside antibiotics at N-methyl-D-aspartate receptors.
Stimulatory and inhibitory properties of aminoglycoside antibiotics at N-methyl-D-aspartate receptors.
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氨基糖苷类抗生素对 N-甲基-D-天冬氨酸受体的刺激和抑制特性。
DOI：
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发表时间：
1999
影响因子：
3.5
通讯作者：
K. Igarashi
中科院分区：
文献类型：
--
作者：
T. Masuko;T. Kuno;K. Kashiwagi;T. Kusama;K. Williams;K. Igarashi
使用电压钳记录非洲爪蟾卵母细胞中表达的重组 NMDA 受体，研究氨基糖苷类抗生素对 N-甲基-D-天冬氨酸 (NMDA) 受体的影响。研究发现许多氨基糖苷类药物可以增强异聚 NR1A/NR2B 受体的宏观电流，但不能增强 NR1A/NR2A、NR1A/NR2C、NR1A/NR2D 或 NR1B/NR2B 受体的宏观电流。增强程度依次为新霉素B>巴龙霉素>庆大霉素C>遗传霉素>卡那霉素A>链霉素。春雷霉素和壮观霉素未见增强作用。刺激程度与氨基糖苷类中氨基的数量相关。氨基糖苷类的刺激作用在甘氨酸的亚饱和浓度和酸性pH下更加明显，类似于精胺的刺激作用。我们测量了氨基糖苷类药物对突变型 NMDA 受体的影响，以确定 NMDA 受体亚基中的哪些氨基酸残基参与刺激。减少或消除精胺刺激的突变也减少了氨基糖苷类的刺激。几种氨基糖苷类药物对 NMDA 受体产生微弱的电压依赖性阻断，但抑制程度似乎与分子中氨基的数量无关。结果表明，具有三个以上氨基的氨基糖苷类具有通过 NMDA 受体上的精胺结合位点介导的刺激作用。
The effects of aminoglycoside antibiotics on N-methyl-D-aspartate (NMDA) receptors were studied using voltage-clamp recording of recombinant NMDA receptors expressed in Xenopus oocytes. A number of aminoglycosides were found to potentiate macroscopic currents at heteromeric NR1A/NR2B receptors, but not at NR1A/NR2A, NR1A/NR2C, NR1A/NR2D, or NR1B/NR2B receptors. The degree of potentiation had a rank order neomycin B > paromomycin > gentamicin C > geneticin > kanamycin A > streptomycin. Potentiation was not seen with kasugamycin and spectinomycin. The degree of stimulation paralleled the number of the amino groups in the aminoglycosides. The stimulatory effects of aminoglycosides were more pronounced at subsaturating concentrations of glycine and at acidic pH, similar to the stimulatory effects of spermine. We measured the effects of aminoglycosides at mutant NMDA receptors to determine which amino acid residues in NMDA receptor subunits are involved in stimulation. Mutations that reduced or abolished spermine stimulation also reduced stimulation by aminoglycosides. Several aminoglycosides produced a weak voltage-dependent block of NMDA receptors, but the degree of inhibition did not appear to correlate with the number of amino groups in the molecule. The results suggest that aminoglycosides having more than three amino groups have stimulatory effects that are mediated through the spermine-binding site on NMDA receptors.
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影响因子：
3.6
作者：
K. Kashiwagi;J. Fukuchi;J. Chao;K. Igarashi;K. Williams
通讯作者：
K. Kashiwagi;J. Fukuchi;J. Chao;K. Igarashi;K. Williams
影响因子：
3.6
作者：
K. Williams
通讯作者：
K. Williams
N-甲基-D-天冬氨酸受体中的一种酸性氨基酸，对精胺刺激很重要。
DOI：
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发表时间：
1995
期刊：
Molecular pharmacology.
影响因子：
--
作者：
Williams,K;Kashiwagi,K;Fukuchi,J;Igarashi,K
通讯作者：
Igarashi,K
DOI：
10.1073/pnas.90.14.6731
发表时间：
1993-07-15
影响因子：
11.1
作者：
DURAND, GM;BENNETT, MVL;ZUKIN, RS
通讯作者：
ZUKIN, RS
影响因子：
56.9
作者：
TRAYNELIS, SF;HARTLEY, M;HEINEMANN, SF
通讯作者：
HEINEMANN, SF