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

虽然新生儿肾脏在尿液中浓缩尿液中的这种矛盾的不成熟，但我们研究了Henle循环的功能，并在新生儿小管的内部延髓中收集了鸭子（IMCD），在膜的内部含量的mrna expormenters和Immunofluorescenters和Immunofluorescenters和Immunofluorescenters，Immunofluorescenters和Immunofluorescentercenters和Immunofluorescenterccenters，又调查了Henle浓度的不成熟。在新生儿和成人肾脏Sliss中，还进行了使用多克隆抗体的E RCCC2和RCLC -K1。在第1天的ding肢（TALS）和IMCDS中为14.6 + 1.1 mV（n = 27）和42.7 + 6.1 MV（n = 14）。 ，设计四肢（TDL）中的VT在第1天为零。统计中的VTs强烈抑制固醇固体剂量……更大，表明存在NaCl的重吸收力学，类似于与该insensiti ve to insensiti ve chlide通道相似的。阻滞剂5-硝基-2-（3-苯基丙基氨基氨基） - 苯甲酸盐（NPPB）IMCD中的VTS在第1天强烈抑制了TDL和TAL，TDL和TAL都无法对整个循环的水y y IMCDS中的渗透率（PDW）和尿素通透性（PUREA）在第1天表示对尿素的不渗透性和尿素。加压素（1 nmol/L）刺激仅PDW是14天的感官性opressin。 NaCl的尿素引起了新生儿IMCD的易忽略的水通量，表明在新生儿IMCD中的尿素依赖性体积通量。在每个新生小管中，这些新生小管中的特性术都是Quair肾脏中的高音，包括MRNA和IMMNAS和IMMNAS和ImmunofluoreCenters的识别。 1，RCCC-K1，RCLC-K1，RCLC-K1 RENACB亚基，RAQP-2和RUT-A1支持这些发现髓质的髓质小管组织的定性变化主要导致哺乳动物新生儿中未成熟的尿液浓缩能力