Tubuloglomerular feedback and renal function in mice with targeted deletion of the type 1 equilibrative nucleoside transporter
Tubuloglomerular feedback and renal function in mice with targeted deletion of the type 1 equilibrative nucleoside transporter
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DOI：
10.1152/ajprenal.00581.2012
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发表时间：
2013-02-01
影响因子：
4.2
通讯作者：
Schnermann, Jurgen
中科院分区：
文献类型：
--
作者：
Li, Lingli;Mizel, Diane;Schnermann, Jurgen
Li L，Mizel D，Huang Y，Reinner C，Hoerl M，Thiel M，Schnermann J. Tubuloglomerular feedback and renal function in mice with targeted deletion of the type 1 equilibrative nucleotide transporter.美国肾脏生理学杂志304：F382-F389，2013年。首次发表于2012年12月26日; doi：10.1152/ajprenal.00581.2012.- A1腺苷受体（A1 AR）是调节传入小动脉张力所需的管腔NaCl浓度的变化，这意味着细胞外腺苷浓度需要与NaCl同步变化。本实验在主要平衡型核苷转运蛋白ENT 1基因无效突变的小鼠中进行，以测试细胞摄取腺苷对腺苷处置的干扰是否可以改变TGF特征。在具有C57 Bl/6或SWR/J遗传背景的小鼠中测量停止流压（PSF）对最大流刺激的反应。与野生型（WT）小鼠相比，最大流量刺激使ENT 1（-/-）小鼠的PSF降低了1.6 +/- 0.4 mmHg（n = 28）和5.8 +/- 1.1 mmHg（n = 17; P < 0.001），C57 B1/6和1.4 +/- 0.4 mmHg（n = 15）和9 +/- 1.5 mmHg（n = 9; P < 0.001）。ENT 1（-/-）小鼠的腺苷和肌苷血浆浓度显著高于WT小鼠（ADO：1，179 +/-78和225 +/-48 pmol/ml; INO：179 +/-24和47.5 +/-9 pmol/ml）。WT和ENT 1（-/-）小鼠肾脏四种腺苷受体、ENT 2和腺苷脱氨酶的mRNA表达无显著差异。ENT 1（-/-）组肾小球滤过率和平均动脉压无显著性差异，而血浆肾素浓度和心率显著降低。总之，TGF的反应显着衰减在ENT 1的情况下，指出在NaCl-同步变化的细胞外腺苷水平的肾小球体中的核苷转运的作用。
Li L, Mizel D, Huang Y, Eisner C, Hoerl M, Thiel M, Schnermann J. Tubuloglomerular feedback and renal function in mice with targeted deletion of the type 1 equilibrative nucleoside transporter. Am J Physiol Renal Physiol 304: F382-F389, 2013. First published December 26, 2012; doi:10.1152/ajprenal.00581.2012.-A1 adenosine receptors (A1AR) are required for the modulation of afferent arteriolar tone by changes in luminal NaCl concentration implying that extracellular adenosine concentrations need to change in synchrony with NaCl. The present experiments were performed in mice with a null mutation in the gene for the major equilibrative nucleoside transporter ENT1 to test whether interference with adenosine disposition by cellular uptake of adenosine may modify TGF characteristics. Responses of stop flow pressure (PSF) to maximum flow stimulation were measured in mice with either C57Bl/6 or SWR/J genetic backgrounds. Maximum flow stimulation reduced PSF in ENT1(-/-) compared with wild-type (WT) mice by 1.6 +/- 0.4 mmHg (n = 28) and 5.8 +/- 1.1 mmHg (n = 17; P < 0.001) in C57Bl/6 and by 1.4 +/- 0.4 mmHg (n = 15) and 9 +/- 1.5 mmHg (n = 9; P < 0.001) in SWR/J. Plasma concentrations of adenosine and inosine were markedly higher in ENT1(-/-) than WT mice (ado: 1,179 +/- 78 and 225 +/- 48 pmol/ml; ino: 179 +/- 24 and 47.5 +/- 9 pmol/ml). Renal mRNA expressions of the four adenosine receptors, ENT2, and adenosine deaminase were not significantly different between WT and ENT1(-/-) mice. No significant differences of glomerular filtration rate or mean arterial blood pressure were found while plasma renin concentration, and heart rates were significantly lower in ENT1(-/-) animals. In conclusion, TGF responsiveness is significantly attenuated in the absence of ENT1, pointing to a role of nucleoside transport in the NaCl-synchronous changes of extracellular adenosine levels in the juxtaglomerular apparatus interstitium.