Interference of L-arginine analogues with L-arginine transport mediated by the y+ carrier hCAT-2B
Interference of L-arginine analogues with L-arginine transport mediated by the y+ carrier hCAT-2B
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DOI：
10.1006/niox.1996.0106
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发表时间：
1997-02-01
影响因子：
3.9
通讯作者：
Forstermann, U
中科院分区：
文献类型：
--
作者：
Closs, EI;Basha, FZ;Forstermann, U
在非洲爪哇卵母细胞中表达了人诱导型阳离子氨基酸转运蛋白HCAT-2B，并利用该系统检测了几种一氧化氮合酶抑制剂和/或L精氨酸类似物对L精氨酸转运的影响。载体为L-N-G-甲基-L-精氨酸(L-NMA)，不对称L，N-G，N-二甲基-L-精氨酸(L-ADMA)，L-N-5-(1-亚氨基乙基)鸟氨酸(L-NIO)，L-N-G-硝基-L-精氨酸(L-NNA)，L-N-G-硝基-L-精氨酸甲酯(L-NAME)均能抑制细菌脂多糖诱导的264.7巨噬细胞诱导型一氧化氮合酶II的生成。L-NMA、L-ADMA和L-NIO也与L-精氨酸竞争HCAT-2B的运输，而L-NNA和L-NAME没有。对称N-G，N-二甲基-L-精氨酸(L-SDMA)和α-氨基-β-异硫脲戊酸(AITV)和L赖氨酸不能阻断NOSII的酶活性，但能竞争HCAT-2B介导的L-精氨酸转运，并与细胞内的L-精氨酸交换，导致细胞内L-精氨酸的耗竭，而α-氨基-β-异硫脲戊酸是HCAT-2B的底物，对细胞内L-精氨酸的转运几乎没有影响这些数据表明，可诱导的L-精氨酸转运体HCAT-2B和可诱导的NOSII之间的底物识别显著不同，不同的L-精氨酸类似物只对这两种蛋白中的一种或两种具有亲和力，(C)1997年学术出版社。
The inducible human cationic amino acid transporter hCAT-2B was expressed in Xenopus laevis oocytes, and this system was used to test the effect of several NO synthase (NOS) inhibitors and/or L-arginine analogues on L-arginine transport by this y(+) carrier, L-N-G-Methyl-L-arginine (L-NMA), asymmetrical L,N-G, N-G-dimethyl-L-arginine (L-ADMA), L-N-5-(1-iminoethyl)-ornithine (L-NIO), L-N-G-nitro-L-arginine (L-NNA), and L-N-G-nitro-L-arginine methyl ester (L-NAME) all inhibited the inducible NOS II extracted from RAW 264.7 macrophages induced with bacterial lipopolysaccharide. L-NMA, L-ADMA, and L-NIO also competed with L-arginine for transport by hCAT-2B, whereas L-NNA and L-NAME did not. The two L-arginine analogues, symmetrical N-G,N-G-dimethyl-L-arginine (L-SDMA) and alpha-amino-delta-isothioureidovaleric acid (AITV), as well as L-lysine, did not block enzymatic activity of NOS II, but did compete for L-arginine transport mediated by hCAT-2B, L-Lysine and L-SDMA were transported efficiently by hCAT-2B and exchanged against intracellular L-arginine, resulting in an L-arginine depletion of the cells, AITV was a much poorer substrate of hCAT-2B and had only little effect on intracellular L-arginine concentrations, These data indicate that substrate recognition differs markedly between the inducible L-arginine transporter hCAT-2B and the inducible NOS II, with different L-arginine analogues having affinity to only one or both of these proteins, (C) 1997 Academic Press.