1993 Fiscal Year Final Research Report Summary
Mechanism of Biosynthesis and Secretion of Endothelin Family
| Project/Area Number |
03454512
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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 |
内分泌・代謝学
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
HIRATA Yukio Tokyo Medical and Dental University, School of Medicine, Associate Professor, 医学部, 助教授 (50135787)
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| Co-Investigator(Kenkyū-buntansha) |
MARUMO Fumiaki Tokyo Medical and Dental University, School of Medicine, Professor, 医学部, 教授 (00050443)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Endothelin / Regulation of Gene expression / Receptor subtype / Signal transduction / G-protein |
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| Research Abstract |
Objective of the present investigation was to elucidate 1)cellular mechanism by which endothelin-1 (ET-1) is synthesized by and released from vascular endothelial cells and nonvascular cells ; 2) different signal transdutions by endothelin family. ET-1 is constitutively secreted by endothelial and epithelial cells, which is regulated at the transcriptional level. Angiotensin and vasopressin induce phosphatidylinositol turnover to activate protein kinase C and elevate cytosolic calcium level, both of which cause important signals for transactivation of ET-1 gene in endothelial and epithelial cells. ET_A and ET_B receptors are coupled to phospholipase C via Gq protein in vascular smooth muscle cells and endothelial cells, respectively. ET_A receptor is also coupled to adenylate cyclase via Gs protein in vascular smooth muscle cells, while ET_B receptor is also coupled to adenylate cyclase via Gi protein in endothelial cells, suggesting that multiple G-proteins may mediate different sygnals. ET_B receptor in endothelium mediates synthesis of NO, whereas ET_B receptor in vascular smooth muscle, like ET_A receptor, mediates vasoconstriction as well as cell proliferation. Thus, ET receptor subtypes are involved in multiple cell functions via cross-talk of different signal tranduction systems.
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