1991 Fiscal Year Final Research Report Summary
Studies on synthesis, subcellular distribution and release of renin in extrarenal tissues
| Project/Area Number |
01480251
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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 | Fukushima Medical College |
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Principal Investigator |
FUKUCHI Soitsu Fukushima Medical College, Third Department of Internal Medicine, Professor of Medicine, 医学部, 教授 (60004769)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUNO Kenji Fukushima Medical College, Third Department of Internal Medicine, Associate Prof, 医学部, 助教授 (20128557)
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| Project Period (FY) |
1989 – 1991
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| Keywords | Renin / Angiotensin I / Angiotensin II / Vascular Tissue / Neuronal cell / Adrenal cortex / Converting enzyme inhibitor / Renin inhibitor |
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| Research Abstract |
1. By differential centrifugation of rat adrenal cortex, renin was found to be localized mainly in heavy mitochondrial fraction. Further centrifugation of this fraction by Percoll density gradient separated renin in a denser region which was apparently not associated with either mitochondria or lysosomes. In organ-cultured adrenal cortex, renin was found to be released in a time-dependent fashion. The renin was released by angiotensin II (Ang. II), calcium ionophore or endothelin, but not by ACTH.
2. The subcellular distribution and behavior of renin was examined in neuroblastoma cells (N-2a). By differential centrifugation, renin was found to be localized in mitochondrial fraction. By Percoll density centrifugation of this fraction, renin was localized in two compartments with molecular weight of 40 K and both renins were not associated with either mitochondria or lysosomes. The findings were confirmed by reninlabelling experiments using ^<35>S-methionine. Pulse labelling analysis showed that renin in these organelles was released into culture medium time-dependently.
3. Release of renin, as well as angiotensin I (Ang. I) and Ang. II were examined in isolated perfused rat hind legs and human umbilical cord veins. While renin or reninlike activity was not detected at all in the perfusate from either preparation, Ang. I and Ang. II were found to be released continuously for several hours in the absence of external supply of angiotensinogen. In the isolated hind legs release of Ang. II was clearly suppressed by converting enzyme (ACE) inhibitors and prostaglandin synthesis inhibitors, but not by adrenergic antagonist. Similarly, release of Ang. II from the umbilical veins was suppressed by ACE inhibitors.
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