Amino acids as modulators of endothelium-derived nitric oxide
Amino acids as modulators of endothelium-derived nitric oxide
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DOI：
10.1152/ajprenal.00417.2005
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发表时间：
2006-08-01
影响因子：
4.2
通讯作者：
Mattson, David L.
中科院分区：
文献类型：
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作者：
Kakoki, Masao;Kim, Hyung-Suk;Mattson, David L.
为了研究氨基酸调节肾脉管系统中一氧化氮 (NO) 产生和血流的机制，当向灌注液中添加不同的氨基酸时，使用化学发光技术对分离的灌注大鼠肾脏的肾静脉流出物中的 NO 进行定量。向灌注液中添加 10(-4) 或 10(-3) M 阳离子氨基酸（L-鸟氨酸、L-赖氨酸或 L-高精氨酸）或中性氨基酸（L-谷氨酰胺、L-亮氨酸或 L-丝氨酸）可减少 NO 并增加肾血管阻力。阴离子氨基酸（L-谷氨酸或L-天冬氨酸）灌注对这两个参数均没有影响。阳离子和中性氨基酸的作用可以用10(-3) M L-精氨酸逆转，并通过去内皮化或NO合酶抑制来阻止。中性氨基酸而非阳离子氨基酸的作用取决于细胞外钠。在培养的 EA 中，通过 DAF-FM-T 荧光评估，阳离子和中性氨基酸也可减少钙霉素诱导的 NO。 hy926内皮细胞。通过阳离子氨基酸转运蛋白 1 或 CD98/4F2 重链的 siRNA 对系统 y(+) 或 y(+) L 的抑制减弱了这些氨基酸的 NO 消耗作用。最后，培养细胞中的转运研究表明，细胞外空间中的阳离子或中性氨基酸会刺激 L-精氨酸流出细胞。因此，本实验证明，阳离子和中性氨基酸可以通过y(+)和y(+) L转运机制改变细胞L-精氨酸转运，从而调节内皮细胞中NO的产生。
To examine the mechanisms whereby amino acids modulate nitric oxide ( NO) production and blood flow in the renal vasculature, chemiluminescence techniques were used to quantify NO in the renal venous effluent of the isolated, perfused rat kidney as different amino acids were added to the perfusate. The addition of 10(-4) or 10(-3) M cationic amino acids (L-ornithine, L-lysine, or L-homoarginine) or neutral amino acids (L-glutamine, L-leucine, or L-serine) to the perfusate decreased NO and increased renal vascular resistance. Perfusion with anionic amino acids (L-glutamate or L-aspartate) had no effect on either parameter. The effects of the cationic and neutral amino acids were reversed with 10(-3) M L-arginine and prevented by deendothelialization or NO synthase inhibition. The effects of the neutral amino acids but not the cationic amino acids were dependent on extracellular sodium. Cationic and neutral amino acids also decreased calcimycin-induced NO, as assessed by DAF-FM-T fluorescence, in cultured EA. hy926 endothelial cells. Inhibition of system y(+) or y(+) L by siRNA for the cationic amino acid transporter 1 or the CD98/4F2 heavy chain diminished the NO-depleting effects of these amino acids. Finally, transport studies in cultured cells demonstrated that cationic or neutral amino acids in the extracellular space stimulate efflux of L-arginine out of the cell. Thus the present experiments demonstrate that cationic and neutral amino acids can modulate NO production in endothelial cells by altering cellular L-arginine transport through y(+) and y(+) L transport mechanisms.