1995 Fiscal Year Final Research Report Summary
Development of the drug which prevents the induction of acute renal failure and its clinical application
| Project/Area Number |
05557053
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
MARUMO Fumiaki Tokyo Medical and Dental University, 医学部, 教授 (00050443)
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| Co-Investigator(Kenkyū-buntansha) |
OOTSUKA Minoru Research Institute of Fujisawa Pharmacoceutycal Co.Chief Investigator, 主任研究員
SASAKI Sei Tokyo Medical and Dental University, Associate Professor, 医学部, 助教授 (60170677)
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| Project Period (FY) |
1993 – 1995
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| Keywords | Endothelin / Kidney / Renal failure / 受容体 / 抗体 |
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| Research Abstract |
In this research, we intended t o clarify the role of entothelins (ET) and their receptors in the progression of acute renal failure, and to develop the priventive drug for acute renal failure which inhibits the action of ET.
The research has been performed well in respect of clarifying the role of ET in acute renal failure. ET3 is expressed in almost all parts of the kidney, suggesting its important role in kidney function (Ref.1). ET1 production in collectiong duct cells is subjects to many stimulus such as hyperosmolality (Ref.2). ET3 stimulates NO synthesis in glomerular mesangial cells which in turn stimulats cGMP production. These events establish the importance of ET in regulation of kidney functions.
Based on these findings we have tried to raise antibodies against ET receptors (mainly, ETA recptor) which inhibits ET action. We immunized rabbits using several different methods, and obtained a number of antibodies. However, none of these antibodies inhibited the action of ET in kidney fuunction, although some of them recongnised the receptors. It is a general rule that obtaining a good antibody for hydrophobic hormone receptor is extremely difficult. We should try further to obtain a good antibody, but alternative approaches may be considered.
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