| Project/Area Number |
01870111
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Faculty of Medicine, University of Tokyo |
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Principal Investigator |
ENDOU Hitoshi Department of Pharmacology, Faculty of Medicine, University of Tokyo, 医学部(医), 助教授 (20101115)
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| Co-Investigator(Kenkyū-buntansha) |
ENDOU Hitoshi Department of Pharmacology, Faculty of Medicine, University of Tokyo Associate P (20101115)
鄭 圭鎔 東京大学, 医学部, 外国人研究員
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| Project Period (FY) |
1989 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥12,300,000 (Direct Cost: ¥12,300,000)
Fiscal Year 1991: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1990: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1989: ¥7,200,000 (Direct Cost: ¥7,200,000)
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| Keywords | Isolated nephron / PAN nephrosisis / Glomerular epithelium / Angiotensin II / Antidiuretic hormone / Cytosolic free calcium / Endothelin / Lipid peroxidation / 脂質過酸化 / バゾプレシン / 昇汞 / ブラディキニン / Cキナ-ゼ / マイクロパンクチャ- / 実験ネフロ-ゼ / Puromycin aminonucleoside / 活性酸素 / ル-プ利尿薬 / プロスタグランジンE_2 / 細胞内ATP代謝回転 / 高血圧自然発症ラット |
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| Research Abstract |
l. Characteristies of nephron heterogeneity supporting screening systems tor the evaluation of renal drug actions.
The results obtained include nephron energy metabolism, localization of purine-metabolizing enzymes, inhibitory effect of CAMP on superoxide generation in gloseruli, biphasic increasing effect of angiotensin I]on cytosolic calcium transient in early proximal tubule, a novel vasopressin receptor in the proximal tubule, localization of glycine avidinotransferase within the kidney, lipid peroxidation in rat nephron segments, and intrarenal handling of proteins in rats.
2. Screening systems for the evaluation of kidney-acting drugs.
Intrarenal sites of PGE2 production are highly heterogeneous, and loop diuretics increase PGE2 accuiu'ation selectively in the thick ascending limb suggesting PGE2 as a possible physiological mediator to cause diuresis. Furosemide also acts on short loop of descending thin limb, but not on Ions loop, that could be concluded by determining ATP turnover
… More
using isolated nephron seg2ents. Antinephrotic drugs potentiate adenosine action on glo2eruli which is well correlated with 'suppressive effect on free radical formation. Estimation of intranephron lipid peroxidation makes it possible to identify the early proximal tubule as a causative site of early stage in diabetic nephropathy. Frog urinary bladde can be used to identify intra cellular nechanislis of renal drug action especially on sodium ion transport coupled with protein kinase C.
3. Screening systems for the evaluation of nephrotoxicity.
Intracellular ATP turnover and agonist-induced cytosolic free calcium transients are sensitive and useful determinants to quantify nephrotoxicity along the nephron. Metabolic functions such as renal gluconeogenesis and ammoniagenesis can be used to find very early signs of nephrotoxicity prior to histological alterations.
The above-summarized results can not only classify kidney-acting and nephrotoxic drugs, but also bring notable informations for the better understanding nechanisums of these drug actions. Less
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