| Co-Investigator(Kenkyū-buntansha) |
ARAKI Tsutomu Tohoku University, Pharmaceutical Science, Associate Profesesor, 大学院・薬学研究科, 助教授 (80323038)
IMAI Yutaka Tohoku University, Pharmaceutical Science, Professor, 大学院・薬学研究科, 教授 (40133946)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
We investigated the expressional regulation of sodium transporters in the renal tubule, bumetanide-sensitive sodium co-transporter (BSCI) and epithelial sodium channel (ENaC), and the clinical implication of altered expression of genetic mutations of these trarsporters of kidney specific sodium transporter, rBSCI, in the thick ascending limb of Henle.
BSCI is located in thick ascending limb of Henle, and supplies sodium for osmotic gradient, which promotes water re-absorption for urinary concentration. To investigate the expressioral regulation of BSCI, we used a rat model of congenital diabetes insipidus. The results demonstrated the presence of two regulatory mechanisms, vasopressin-dependent and -independent BSCI expression (Kidney Int. 2003 in press), confirming that expressional regulation of this transporter is required for urinary concentration and body fluid regulation. We also reported that the altered BSCI expression is involved in the Lithium nephropathy (Kidney Int. 63:165, 2003) and in chronic renal failure (Nephron Physiol 93:34, 2003), both of which are diseases of urinary concentrating defect.
ENaC is located in distal truble or collecting duct, and its genetic-mutations induce Liddle's syndrome (congenital hypertension). Thus, we examined the presence of genetic polymorphisms of this sodium channel in the general Japanese populatjon. We found several mutations, 3 sense mutations and 5 non-sense mutations, most of which are specific for Japanese population (Clin Exp Nephrol 6:130, 2002). Fortunately, none of mutations were significantly associated with hypertension in the Japanese population (Am J Hypertens 15:189, 2002).
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