Role of renin substrate in the pressor mechanism and physiological significance of des-angiotensin I renin substrate
| Project/Area Number |
60480231
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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 |
Circulatory organs internal medicine
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| Research Institution | Ehime University |
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Principal Investigator |
HIWADA Kunio Ehime University Associate Professor, 医学部, 助教授 (00108391)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIMOTO Akihide Ehime University Associate, 医学部附病院, 助手 (60172855)
HAMADA Mareomi Ehime University Lecturer, 医学部附属病院, 講師 (30127906)
MURAKAMI Eiki Ehime University Lecturer, 医学部附属病院, 講師 (90110832)
TAKADA Yasuharu Ehime University ex-Lecturer, 医学部附属病院, 元講師 (20127898)
NISHIMURA Kazutaka Ehime University ex-Lecturer, 医学部附属病院, 元講師 (70036482)
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| Project Period (FY) |
1985 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1987: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1986: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1985: ¥3,600,000 (Direct Cost: ¥3,600,000)
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| Keywords | Renin substrate / Des-angiotensin I renin substrate / High molecular weight renin substrate / Pregnant woman / Renin / レニン阻害剤アフィニティカラム / 抗ヒトレニン基質抗体アフィニティーカラム |
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| Research Abstract |
The renin-angiotensin system plays an important role in the regulation of blood pressure, and water and electrolyte balance. In this study we measured plasma renin substrate concentration in normal subjects, pregnant women and hemodyalysis patients using the direct and indirect methods. The values measured by the direct assay always showed higher than that by the indirect assay. This was due to the cross-reaction of the antibody to renin substrate with des-angiotensin I renin substrate. A high PRA in pregnant women is due to higher levels of plasma renin substrate and a high PRA in hemodyalysis patients is due to higher levels of plasma renin concentration.
A high molecular weight renin substrate (Mr. 332K daltons) was prepared from plasma of pregnant women. The molecular weight was reduced to 81K by treatment with dithiothreitol (DTE), but not by treatment with SDS. DTT-treated high molecular weight renin substrate was very similar to low molecular weight renin substrate. The antibody against low molecular weight renin substrate completely crossreacted with high molecular weight renin substrate. Our results suggest that high molecular weight renin substrate is probably a complex of low molecular weight renin substrate and other protein(s) which might be bound by disulfide bond.
We prepared an affinity column using a specific human renin inhibitor (ES-305) as a ligand and purified stable human renin from kidneys. We also purified human renin substrate from plasma pool by the modified our previous method. Des-angiotensin I renin substrate was prepared by incubating the purified human renin substrate with the purified renin. The physiological significance of des-angiotensin I renin substrate is under investigation.
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Report
(2 results)
Research Products
(6 results)
