| Project/Area Number |
10218211
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
MINAMINO Naoto National Cardiovascular Center Research Institute, Director, Department of Pharmacology, 薬理部, 部長 (50124839)
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| Co-Investigator(Kenkyū-buntansha) |
KATAFUCHI Takeshi National Cardiovascular Center Research Institute, Research Staff, Laboratory of Development and Evaluation of biomedical Instruments and Systems, 研究機器管理室, 室員 (50300976)
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| Project Period (FY) |
1998 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥65,700,000 (Direct Cost: ¥65,700,000)
Fiscal Year 2002: ¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 2001: ¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 2000: ¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 1999: ¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 1998: ¥13,500,000 (Direct Cost: ¥13,500,000)
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| Keywords | adrenomedullin / inflammation / calcitonin gene-related peptides / proliferation / cytokines / calcitonin receptor-stimulating peptide / plasma calcium-reducing activity / skin / 炎症性サイトカイン / 繊維芽細胞 / 成長因子 / 受容体 / 血管平滑筋細胞 / 産生調節 / 線維芽細胞 / CGRP / 受容体活性調節蛋白 / 上皮細胞 / TNF-α / 炎症反応 / 全身性炎症反応症候群 / IL-1β / 敗血症性ショック / マクロファージ / インターロイキン6 / 腫瘍壊死因子 / 遺伝子発現調節 |
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| Research Abstract |
To elucidate the regulatory effects of adrenomedullin (AM) in the inflammation and proliferation, we investigated its effects on primary cultured rat skin fibroblasts and keratinocytes. AM suppressed proliferation of the fibroblasts in the presence of 1% fetal bovine serum and regulated the production of cytokines and growth factors in them. AM production in the fibroblasts was dynamically regulated by cytokines, hormones and inflammation-related reagents, while that in the keratinocytes remained unchanged by these substances. The receptors expressed on the fibroblasts were specific for AM, while those on the keratinocytes for calcitonin gene-related peptide (CGRP). Taken together, AM in the skin is deduced to regulate the vasodilation, proliferation, production of cytokines and growth factors mainly through the fibroblasts.
By monitoring the cAMP production in LLC-PK_1 of a pig renal epithelial cell line, we screened new peptides in the acid extracts of pig brain. We found several candidates of unidentified bioactive peptides, and finally purified one peptide. By structural analysis, this peptide was verified to be a 38-residue peptide with a C-terminal amide and a disulfide linkage, and showed higher sequence homology to CGRP. This peptide reduced the plasma calcium concentration instead of the blood pressure, and stimulated the calcitonin (CT) receptor at the potency much higher than that of CT. Thus, we designated it as CT receptor-stimulating peptide (CRSP). The discovery of CRSP led us to recognize the complexity of the CT/CGRP superfamily that consists of CT, CGRP, AM, amylin and CRSP.
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