Regulation of ecto-5'-nucleotidase by NaCl and nitric oxide: potential roles in tubuloglomerular feedback and adaptation.
Regulation of ecto-5'-nucleotidase by NaCl and nitric oxide: potential roles in tubuloglomerular feedback and adaptation.
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氯化钠和一氧化氮对 ecto-5-核苷酸酶的调节：在肾小球反馈和适应中的潜在作用。
DOI：
10.1152/ajprenal.00043.2006
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Blantz,RolandC
中科院分区：
文献类型：
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作者：
Satriano,Joseph;Wead,Lucinda;Cardus,Anna;Deng,Aihua;Boss,GerryR;Thomson,ScottC;Blantz,RolandC
肾小管肾小球反馈（TGF）系统用于在肾小管重吸收和肾小球滤过率（GFR）之间建立适当的平衡。致密斑处的高盐激活TGF以降低GFR。TGF信号的效应分子包括ATP和腺苷。随着时间的推移，即使高盐浓度持续存在，GFR也会通过增加来适应。这种TGF适应的潜在调节剂是一氧化氮合酶-1衍生的一氧化氮（NO）。在离体肾小球制备物中，我们开发了一个系统，用于评估改变饮食盐对外-5 ′-核苷酸酶（ecto-5′-NT）活性的影响，外-5 ′-NT是ATP转化为腺苷的最终酶。我们在离体肾小球中发现了可观察到的ecto-5′-NT活性，并且这种活性可以被膳食盐调节，具有高盐增加活性。相反，NO降低肾小球制备物中的外膜-5 ′-NT活性。此外，NO抑制外-5 ′-NT活性在二硫苏糖醇的存在下被抑制，表明亚硝基化是一种可逆的氧化应激敏感机制。盐诱导的ecto-5′-NT活化与TGF高盐重置相关。NO对酶活性的抑制可能是适应期的一部分。
The tubuloglomerular feedback (TGF) system serves to establish an appropriate balance between tubular reabsorption and glomerular filtration rate (GFR). High salt at the macula densa activates TGF to decrease GFR. Effector molecules for the TGF signal include ATP and adenosine. Over time, the GFR will adapt by increasing even if a high salt concentration persists. A potential modulator of this TGF adaptation is nitric oxide synthase-1-derived nitric oxide (NO). In isolated glomerular preparations, we developed a system for evaluating the effects of changing dietary salt on ecto-5′-nucleotidase (ecto-5′-NT) activity, the final enzyme in the conversion of ATP to adenosine. We found observable ecto-5′-NT activity in isolated glomeruli and that this activity can be regulated by dietary salt, with high salt increasing activity. Conversely, NO decreases ecto-5′-NT activity in glomerular preparations. Moreover, NO inhibition of ecto-5′-NT activity is suppressed in the presence of dithiothreitol, suggesting nitrosylation as a reversible, oxidative stress-sensitive mechanism. The salt-induced activation of ecto-5′-NT correlates with high salt resetting of TGF. NO inhibition of enzymatic activity could be part of the adaptive phase.