1988 Fiscal Year Final Research Report Summary
The role of kallikrein inhibitor in the regulation of the renal kallikrein-kinin system activity
| Project/Area Number |
60480235
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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 | Sapporo Medical University |
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Principal Investigator |
SHIMAMOTO Kazuaki Sapporo Medical College, Associate Professor, 医学部, 助教授 (40136940)
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| Co-Investigator(Kenkyū-buntansha) |
吉田 茂夫 札幌医科大学, 医学部, 講師 (30136965)
TANAKA Shigemichi Sapporo Medical College, Assistant Professor, 医学部, 講師 (50163522)
SHOJI Tetsuro Sapporo Medical College, Assistant Professor, 医学部, 講師 (60154340)
KIKUCHI Kenjiro Sapporo Medical College, Associate Professor, 医学部, 助教授 (30045455)
YOSHIDA Shigeo Sapporo Medical College, Assistant Professor
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| Project Period (FY) |
1985 – 1987
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| Keywords | Kallikrein / Kallikrein-inhibitor / Essential Hypertension / Renal Depressor System / Low Renin Essential Hypertension / Chronic Glomerulonephritis / 酵素比活性 |
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| Research Abstract |
Urinary excretions of kallikrein quantity and activity were significantly lower in patients with both essential hypertension and those with chronic glomerulonephritis. The specific activity calculated from enzyme activity divided by quantity was significantly lower in both patient groups than in the normal control,suggesting that the inhibited activity of renal kallikrein in these diseases may be caused by both the suppression of enzyme production and enzyme activity. Therefore, the possibility was investigated whether the kallikrein inhibitors may have a connection in the mechanism of the suppressed activity of kallikrein. After elution of urine samples in Sephadex G-200 column chromatography,any substance which inhibits the kallikrein activity was not detected in patient samples. Kallikrein activity and quantity revealed a single peak,and other peaks were not found in this study. However,the specific activity in each fractionations represented the significant lower values in the part of early fractionations of peak than in later,but no difference in normal control,suggesting that the kallikrein inhibitor with low molecular weight remains in both diseases. In the study by polyacrylamide gel electrophoresis, (PAGE) and Western Blot analysis,only one band was observed in patient's samples as well as the normal control,and an abnormal band was not detected.
In rat experiments,both urinary excretions of kallikrein quantity and activity were significantly increased and decreased in DOCA-salt hypertension or 5/6 renoprival hypertension,respectively. Howeverthere was no significant difference found in kallikrein specific activity between the normal control and the experimental groups. This data suggests that the kallikrein-inhibitor does not play an important role in the rat kidney and that the regulation of this system activity may be performed mainly in the enzyme production step.
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