A new hypothesis on the maturation of urea-dependent urine concentrating mechanism

尿素依赖性尿液浓缩机制成熟的新假说

• 批准号: 11670734
• 负责人: KONDO Yoshiaki
• 金额: $ 2.43万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670734/
• 关键词: urine-concentrating mechanism; kidney medulla; ontogeny; phylogeny; urea; newborn

While neonatal kidneys are not powerful in concentrating urine, they already dilute urine as efficiently as adult kidneys. To elucidate the basis for this paradoxical immaturity in urine-concentrating ability, we investigated the function of Henle' s loop and collecting ducts (IMCDs) in the inner medulla of neonatal rat kidneys.Analyses of individual renal tubules in the inner medulla of neonatal and adult rat kidneys were performed by measurering mRNA expression of membrane transporters, transepithelial voltages, and isotopic water and ion fluxes. Immunofluorescent identification of the rCCC2 and rCLC-K1 using polyclonal antibodies was also performed in neonatal and adult kidney slices.On day 1, the transepithelial voltages (VTs) in the thin ascending limbs (tALs) and IMCDs were 14.6 + 1.1 mV (n=27) and? 42.7 + 6.1 mV (n=14), respectively. The VTs in the thin descending limbs (tDLs) were zero on day 1. The VTs in the tALs were strongly inhibited by luminal bumetanide or basolateral ou … More abain, suggesting the presence of a NaCl reabsorptionmechanism similar to that in the thick ascending limb (TAL). The diffusional voltage (VD) of the tAL due to transepithelial NaCl gradient was almost insensitive to a chloride channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB). The VTs in the IMCDs were strongly inhibited by luminal amiloride.On day 1, both the tDL and tAL were impermeable to water, indicating the water impermeability of the entire loop. Diffusional water permeability (Pdw) and urea permeabilities (Purea) in the IMCDs indicated virtual impermeability to after and urea on day 1. Stimulation by vasopressin (1 nmol/L) revealed that only Pdw was sensitive to vasopressin by day 14. A partial isoosmolar replacement of luminal urea by NaCl evoked negligible water flux across the neonatal IMCDs, indicating the absence of urea-dependent volume flux in the neonatal IMCD.These transport characteristics in each neonatal tubule are similar to those in quail kidneys.Identification of mRNAs and immunofluorescent studies for specific transporters including rAQP-1, rCCC2, rCLC-K1, rENaCb subunit, rAQP-2 and rUT-A1 supported these findings.Conclusion. We propose with reasonable assurance that the renal medullary tubule organization of neonatal rats shares a tremendous similarity with avian renal medulla, and that the qualitative changes in the organization of medullary tubules are primarily responsible for the immature urine-concentrating ability in mammalian neonates. Less

虽然新生儿肾脏在浓缩尿液方面并不强大，但它们已经像成人肾脏一样有效地稀释尿液。为了阐明这种反常的尿浓缩能力不成熟的基础，我们研究了新生大鼠肾脏内髓的亨利氏袢和集合管（IMCD）的功能，通过测量膜转运蛋白mRNA表达、跨上皮电压、同位素水和离子通量来分析新生和成年大鼠肾脏内髓的单个肾小管。在新生儿和成人肾脏切片中，用多克隆抗体进行rCCC 2和rCLC-K 1的免疫荧光鉴定，在第1天，薄升支（tAL）和IMCD的跨上皮电压（VT）分别为14.6 ± 1.1 mV（n=27）和？42.7+6.1mV（n=14）。第1天，细降支（tDL）的VT为零。鲁米那布美他尼或基底外侧口 ...更多信息 abain，提示存在类似于粗升支（TAL）的NaCl重吸收机制。由于跨上皮NaCl梯度引起的tAL的扩散电压（VD）对氯离子通道阻断剂5-硝基-2-（3-苯丙氨基）-苯甲酸酯（NPPB）几乎不敏感。在IMCD中的VT被鲁米那阿米洛利强烈抑制，在第1天，tDL和tAL都不透水，表明整个环的水不透性。IMCD中的扩散水渗透率（Pdw）和尿素渗透率（Purea）表明在第1天对尿素和尿素的虚拟不渗透性。加压素（1 nmol/L）的刺激显示，只有Pdw是敏感的加压素的第14天。用NaCl部分等渗替代管腔尿素，新生鼠IMCD中的水通量可忽略，表明新生鼠IMCD中不存在尿素依赖的体积通量。新生鼠各肾小管中的这些转运特征与鹌鹑肾脏中的那些相似。rAQP-2和rUT-A1支持上述结果。我们提出合理的保证，新生大鼠的肾脏髓质小管组织与鸟类肾脏髓质有着巨大的相似性，并且髓质小管组织的质的变化是哺乳动物新生儿未成熟的尿浓缩能力的主要原因。少