中性氨基酸转运系统L和中枢神经系统电压门控Ca^2通道的功能联系。-猫眼课题宝

中性氨基酸转运系统L和中枢神经系统电压门控Ca^2通道的功能联系。

批准号：

15590143

负责人：

FUJITA Takuya

金额：

$1.98万

依托单位：

Kyoto Pharmaceutical University

依托单位国家：

日本

项目类别：

Grant-in-Aid for Scientific Research (C)

财政年份：

2003

资助国家：

日本

项目状态：

已结题

起止时间：

2003 至 2004

来源：

https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590143/

关键词：

Amino acids Transporter Voltage-gated Ca^<2+> channels Gabapentin Astrocytes Neurons Nitric oxide Nitric oxide synthase 電位依存性Ca^<2+>チャンネル gabapentin アストロサイトニューロン

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英文摘要

In the present research, I have investigated the involvement of Na^+-independent neutral amino acid transport system L in voltage-gated Ca^<2+> channels blocking action by gabapentin in normal human astrocytes and primary cultured mouse cerebrocortical neurons. In particular, there is no information available for amino acid transport system L in neurons that are thought to be a major target site for gabapentin. Therefore, we primarily investigated the functional characteristics of gabapentin transport into the neurons using primary cultures of mouse cerebrocortical neurons. Cerebrocortical neurons were isolated from 15-day-old-fetal ddY mice. The purity of neurons and contamination of glial cells were confirmed by immunocytochemistry using anti-MAP2 (neuronal marker) and anti-GFAP (glial marker) antibodies, respectively.The uptake of [^3H]gabapentin in neurons was predominantly Na^+-independent, was stimulated by lowering the extracellular pH, and was inhibited by hydrophobic neutral amino acids. The transport process was saturable with a K_t of 66±0.7 μM for gabapentin uptake. RT PCR revealed that mouse cerebrocortical neurons express the system L amino acid transporters, LAT1 and LAT2, and the heavy chain of the cell surface antigen 4F2 (4F2hc/CD98), which is required for the functional expression of LAT1 and LAT2. Structurally-related compounds of gabapentin, such as 1-amino-1-cyclohexanecarboxylic acid (ACHC), 1-amino-1-cyclopentane- carboxylic acid (cycloleucine), and BCH inhibited the Na^+-independent gabapentin transport in a concentration-dependent manner, and their IC_<50> values were±13, 185±24, and 56±21 μM, respectively. In addition, preloading of various neutral amino acids into neurons markedly enhanced Na^+-independent [^3H]gabapentin uptake (trans-stimulation effect).These results suggest that functional amino acid transport system L is expressed in mouse cerebrocortical neurons.

期刊论文(47)

专著(0)

科研奖励(0)

会议论文

Functional expression of constitutive nitric oxide synthase regulated by voltage gated Na^+- and Ca^<2+> channels in cultured human astrocytes.

在培养的人星形胶质细胞中，由电压门控Na ^ - 和Ca ^ 2 通道调节的组成型一氧化氮合酶的功能表达。

DOI： --

发表时间： 2004

期刊：

Glia 46

影响因子： --

作者：

[Kazunari Tanaka et al., Tomomi Uchiyama et al., Takuya Fujita et al., Miyuki Wada et al., Kazunari Tanaka et al., Uchiyama Tomomi et al., Takuya Fujita et al., Miyuki Wada et al., Kazunari Tanaka et al., Miyuki Wada et al., Takuya Fujita et al., Tomomi Uchiyama et al., Takuya Fujita et al., Michiko Oka et al.]

通讯作者： Michiko Oka et al.

Functional characterization of brain peptide transporter in rat cerebral cortex:: identification of the high-affinity type H+/peptide transporter PEPT2

DOI： 10.1016/j.brainres.2003.10.049

发表时间： 2004-01-30

期刊：

BRAIN RESEARCH

影响因子： 2.9

作者：

[Fujita, T, Kishida, T, Ganapathy, V]

通讯作者： Ganapathy, V

Functional expression and adaptive regulation of Na^+-dependent neutral amino acid transporter SNAT1/ATA in normal human astrocytes under amino acid starved condition.

氨基酸饥饿条件下正常人星形胶质细胞中Na + 依赖性中性氨基酸转运蛋白SNAT1/ATA的功能表达和适应性调节。