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

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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.