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学机制。我们最近的研究表明，尿液浓缩机制的发育变化不是定量变化，而是定性变化。新生儿发育的核心成分是尿液浓缩系统从唯一的NaCl肿瘤系统到复杂的尿素-NACL积累系统。我们尤其专注于分布在每个肾小管段的钙素感应受体的发展。要分析钙感应受体（CSR）在管状功能调节中的贡献，亨尔循环（MTAL）的髓质厚度升升（MTAL）是微per液的。在新生儿小鼠中，新霉素CSR激动剂略微增加了细胞内Ca活性，而不会从基底外侧改变细胞内pH。基底外侧溶液中的新霉素酸化了成年MTAL的细胞，而对细胞内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DID的抑制。在新生儿肾切片的MTAL中未证明CSR免疫反应性。这些结果强烈表明CSR在新生儿MTAL中没有发展。 CSR对细胞酸化的确切机制将在未来的研究中进行更多分析。