| Project/Area Number |
61480121
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | National Cardiovascular Center |
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Principal Investigator |
IMAI Masashi National Cardivascular Center, 薬理部, 部長 (40049010)
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| Co-Investigator(Kenkyū-buntansha) |
渡辺 卓司 蛋白質研究奨励会ペプチド研究所, 研究員
SHIMA Masaaki National Cardivascular Center, 薬理部, 研究生
KONDO Yoshiaki National Cardivascular Center, 薬理部, 研究生 (00221250)
KOSEKI Chizuko National Cardivascular Center, 薬理部, 研究員 (80134534)
AKABANE Satoshi National Cardivascular Center
WATANABE Takushi Peptide Institute
谷口 淳一 国立循環器病センター, 薬理部, 研究員 (90179838)
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| Project Period (FY) |
1986 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1988: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Keywords | Atrial natriuretic peptide / Renal tubule / Glomerulus / Henle's loop / Renal medullary blood flow / Autoradiography / Receptor / ANP / 尿中Na排泄 / 平滑筋 / エンドペプチターゼ / 心房性ナトリウム利尿ペプチド / 集合管 / 腎髄質 / バゾプレシン / 心房性Na利尿ポリペプチド / ANF / 直血管 / 受容体 / オートラジオグラフィ |
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| Research Abstract |
Interactions between atrial natriuretic peptide(ANP) and the kidney were examined by various approaches including autoradiography, receptor binding study, clearance study, in vitro microperfusion of renal tubules, and others. The following 5 major results were obtained: (1) By sutoradiography, we demonstrated that receptors for ANP were distributed in the glomeruli (foot processes of epithelial cells), vascular bundles and inner medullary collecting tubules. By solubilizing ANP-receptors labeled by photoaffinity method, we found that molecular size of the receptors in the kidney is 65 kD wherease the aorta and the adrenal grand contain two kinds of receptors having different molecular size, 65 kD and 140 kD. (2) The structure-activity relationship, examined by using -hANP analogs, showed that amino acids in N-termainus, amino acid at 12th position and ring structure are essential for physiological effects. (3) Intrarenal arterial administration of ANP in combination with acetyl choline or secretin suggested that effects of ANP are mediated in part by its renal vascular action. (4) In vitro microperfusion of isolated renal tubules failed to demonstrate any effects on NaCl and water transport in segments of Henle's loop and inner medullary collecting tubule. (5) Degradation of ANP, inhibitable with phospholamidone, was localized to both the glomeruli and the proximal tubules.
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