Developmental analyses of Ca transporters and Ca sensing receptors in the kidneys

肾脏中 Ca 转运蛋白和 Ca 感应受体的发育分析

• 批准号: 15390263
• 负责人: KONDO Yoshiaki
• 金额: $ 9.6万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390263/
• 关键词: urine concentrating mechanism; ion transporters; calcium metabolism; renal tubular dysfunction; microperfusion; microfluorometry; 微小灌流法

Urine concentrating mechanism is a biological mechanism that has evolved only in birds and mammals. Our recent studies have revealed that developmental changes of the urine concentrating mechanism are not the quantitative changes but the qualitative changes. The core component of the neonatal development is the transition of the urine concentrating system from the sole NaCl-aocumulating system to the complex Urea-NaCl accumulating system.In the present research project, we analyzed the relationship between neonatal calcium homeostasis and the development of urine-concentrating mechanism. We especially focused on the development of calciuum-sensing receptors distributed to each renal tubule segments.To analyze the contribution of calcium-sensing receptor (CSR) in the regulation of tubular function, the outer medullary thick ascending limbs of Henle's loop (mTAL) were microperfused in vitro. In the neonatal mice, neomycin the CSR agonist slightly increased intracellular Ca activity without changing intracellular pH from the basolateral side. Neomycin in the basolateral solution acidified the cells of the adult mTAL, whereas it had no effect on intracellular Ca activities. Acidification of the cells by neomycin was not inhibited by amiloride or the anion transport inhibitor DIDS. CSR immunoreactivity was not demonstrated in the mTAL of the neonatal kidney slices.These results strongly suggest that the CSR is not developed in the neonatal mTAL. The precise mechanism of acidification of cells by CSR is to be analyzed more in the future studies.

尿液浓缩机制是一种生物学机制，仅在鸟类和哺乳动物中进化。近年来的研究表明，尿浓缩机制的发展变化不是量变，而是质变。新生儿发育的核心是尿浓缩系统从单一的NaCl-尿积累系统向尿素-NaCl复合尿积累系统的转变，本研究分析了新生儿钙稳态与尿浓缩机制的发展之间的关系。本研究通过对离体肾髓外段Henle袢升支（mTAL）的微灌注，探讨钙敏感受体（CSR）在肾小管功能调控中的作用。在新生小鼠中，CSR激动剂新霉素略微增加细胞内Ca活性，而不改变基底侧的细胞内pH。基底外侧溶液中的新霉素使成人mTAL细胞酸化，而对细胞内Ca活性没有影响。阿米洛利或阴离子转运抑制剂DIDS不能抑制新霉素引起的细胞酸化。结果表明，新生大鼠mTAL中未发现CSR免疫反应性，提示新生大鼠mTAL中不存在CSR。CSR酸化细胞的确切机制有待于进一步研究。