SELECTIVE TARGETING OF NITRIC-OXIDE SYNTHASE INHIBITORS TO SYSTEM Y(+) IN ACTIVATED MACROPHAGES
SELECTIVE TARGETING OF NITRIC-OXIDE SYNTHASE INHIBITORS TO SYSTEM Y(+) IN ACTIVATED MACROPHAGES
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DOI：
10.1006/bbrc.1994.1511
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发表时间：
1994-04-29
影响因子：
3.1
通讯作者：
MANN, GE
中科院分区：
文献类型：
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作者：
BAYDOUN, AR;MANN, GE
在小鼠巨噬细胞J774中，研究了介导一氧化氮合酶抑制剂摄取的氨基酸转运系统。用细菌内毒素（LPS, 1 μ g ml(-1), 24 h）处理J774细胞，选择性地增加了n -g-单甲基- l- [C-14]精氨酸（L-NMMA）的转运能力，而n -g-硝基- l [h -3]精氨酸（L-NNA）的转运能力不受影响。抑制研究证实，阳离子转运系统y（+）介导l-精氨酸、L-NMMA和n - g -亚氨基乙基- l-鸟氨酸（L-NIO）的摄取。一种中性转运体，底物特异性低，对LPS不敏感，介导l -瓜氨酸、L-NNA及其甲酯L-NAME的摄取。我们得出结论，在lps刺激的巨噬细胞中，y（+）转运体的表达增强(1)可能有助于诱导型NO合成酶的选择性抑制剂靶向内毒素休克中产生NO的活化细胞。(C) 1994学术出版社，Inc.
Amino acid transport systems mediating uptake of nitric oxide (NO) synthase inhibitors were characterized in the murine macrophage cell line J774. Treatment of J774 cells with bacterial endotoxin (LPS, 1 mu g ml(-1), 24 h) selectively increased the transport capacity for N-G-monomethyl-L-[C-14]arginine (L-NMMA), whereas transport of N-g-nitro-L[H-3]arginine (L-NNA) was unaffected. Inhibition studies established that the cationic transport system y(+) mediates uptake of L-arginine, L-NMMA and N-G-iminoethyl-L-ornithine (L-NIO). A neutral transporter, with low substrate specificity and insensitive to LPS, mediates uptake of L-citrulline, L-NNA and its methyl ester L-NAME. We conclude that enhanced expression of the y(+) transporter in LPS-stimulated macrophages (1) may facilitate the targeting of selective inhibitors of inducible NO synthase to activated cells generating NO in endotoxin shock. (C) 1994 Academic Press, Inc.