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

基本信息

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

项目摘要

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仅在鸟类和哺乳动物中进化的生物机制。我们最近的研究表明，尿液浓缩机制的发育变化不是量变而是质变。新生儿发育的核心组成部分是尿液浓缩系统从单一的氯化钠积累系统向复杂的尿素-氯化钠积累系统的转变。在本研究项目中，我们分析了新生儿钙稳态与尿液发育之间的关系。 ——集中机制。我们特别关注分布在每个肾小管节段的钙敏感受体的发育。为了分析钙敏感受体（CSR）在肾小管功能调节中的贡献，我们对亨利袢的外髓厚升肢（mTAL）进行了研究。体外微灌注。在新生小鼠中，CSR 激动剂新霉素略微增加细胞内 Ca2+ 活性，而不改变基底外侧细胞内 pH 值。基底外侧溶液中的新霉素酸化成体 mTAL 的细胞，但对细胞内 Ca 活性没有影响。新霉素对细胞的酸化不受阿米洛利或阴离子转运抑制剂 DIDS 的抑制。新生儿肾切片的 mTAL 中未显示 CSR 免疫反应性。这些结果强烈表明新生儿 mTAL 中未发育出 CSR。 CSR酸化细胞的确切机制有待今后的研究进一步分析。