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

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15390263
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Tohoku University
• Principal Investigator: KONDO Yoshiaki Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (00221250)
• Co-Investigator(Kenkyū-buntansha): IINUMA Kazuie Tohoku University, Graduate school of Medicine, Professor, 大学院・医学系研究科, 教授 (80004927) ; OOURA Toshihiro Tohoku University, Graduate school of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (10176828) ; MATSUBARA Mitsunobu Tohoku University, Graduate school of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (30282073) ; UCHIDA Shinichi Tokyo Medical and Dental University, Graduate school of Medicine, Lecture, 大学院・医学研究科, 講師 (50262184) ; FUJIWARA Ikuma Tohoku Unversity, Hospital, Lecture, 病院・講師 (10271909)
• Project Period (FY): 2003 – 2004
• Keywords: urine concentrating mechanism / ion transporters / calcium metabolism / renal tubular dysfunction / microperfusion / microfluorometry

Research Abstract

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.