| Project/Area Number |
10218210
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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 | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
UETA Yoichi (2000-2002) University of Occupational and Environmental Health, Department of Physiology, Professor, 医学部, 教授 (10232745)
山下 博 (1998-1999) 産業医科大学, 医学部, 教授 (00030841)
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| Co-Investigator(Kenkyū-buntansha) |
NOGUCHI Jun University of Occupational and Environmental Health, Department of Physiology, Research Associate, 医学部, 助手 (00330978)
YAMASHITA Hiroshi Kyushu Nutrition Welfare University, Professor, 食物栄養学部, 教授 (00030841)
上田 陽一 産業医科大学, 医学部, 講師 (10232745)
澁谷 泉 産業医科大学, 医学部, 助教授 (50162649)
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| Project Period (FY) |
2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥47,200,000 (Direct Cost: ¥47,200,000)
Fiscal Year 2002: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 2001: ¥8,400,000 (Direct Cost: ¥8,400,000)
Fiscal Year 2000: ¥9,900,000 (Direct Cost: ¥9,900,000)
Fiscal Year 1999: ¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 1998: ¥11,200,000 (Direct Cost: ¥11,200,000)
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| Keywords | adrenomedullin / blood-brain barrier / endothelial cells / central nervous system / cerebrospinal fluid / tight junction / stress / アドレノメデュリン / グリア細胞 / mRNA / RT-PCR怯 / RAMP-1,-2,-3 / 視床下部 / オキシトシン / バゾプレッシン / Fos蛋白 / 血圧 / 室傍核 / 視索上核 / 自律神経 / 神経内分泌 |
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| Research Abstract |
Adrenomedullin (AM) isolated from the human pheochromocytoma is one of the potent hypotensive peptides. The purpose of the present study is to examine the physiological role of AM in the central nervous system (CNS). We have demonstrated that rat cerebral endothelial cells produce and secrete large amount of AM in vitro blood-brain barrier (BBB) preparation. The results obtained this year are as follow.
(1) The concentrations of AM in plasma collected from the jugular vain, the carotid artery and suprarenal posterior vena cava were measured in rats anesthetized with sodium pentbarbi tal. The highest concentration of AM in plasma was collected samples from the jugular vein.
(2) Percutaneous cisternal cerebrospinal fluid (CSF) taps were performed in rats to determine the concentration of AM in the CSF. The concentration of AM in the CSF of rats anesthetized with ether showed higher than those with isoflurane. The concentration of AM in the CSF increased over 3-4 folds higher than the control at 5 and 7 days during drinking 2% saline.
(3) Chronic AM exposure increase transendothelial electrical resistance in vitro BBB, suggesting a tightening of intercellular junctions. There was no significant effect of AM on the expression of tight junction proteins (claudin-1, occludin and ZO-1). Chronic AM treatment in vitro BBB may influence the localization of these proteins without a change in protein expression.
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