The localization and physiological role of adrenomedullin and related-peptides in the central nervous system

肾上腺髓质素及相关肽在中枢神经系统中的定位和生理作用

• 批准号: 10218210
• 负责人: UETA Yoichi
• 金额: $ 30.21万
• 依托单位: University of Occupational and Environmental Health, Japan
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10218210/
• 关键词: 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

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.

从人嗜铬细胞瘤中分离出的肾上腺髓质素 (AM) 是一种有效的降血压肽。本研究的目的是检查 AM 在中枢神经系统 (CNS) 中的生理作用。我们已经在体外血脑屏障（BBB）制剂中证明大鼠脑内皮细胞产生并分泌大量AM。今年的研究结果如下：(1)用戊巴比妥钠麻醉大鼠，测定颈静脉、颈动脉和肾上后腔静脉血浆中AM的浓度。颈静脉采集血浆中AM浓度最高。(2)对大鼠进行经皮脑池脑脊液(CSF)穿刺，测定CSF中AM的浓度。乙醚麻醉大鼠脑脊液中 AM 浓度高于异氟醚麻醉大鼠。在饮用2%盐水的第5天和第7天，脑脊液中AM的浓度比对照增加了3-4倍。(3)长期接触AM会增加体外BBB的跨内皮电阻，表明细胞间连接收紧。 AM 对紧密连接蛋白（claudin-1、occludin 和 ZO-1）的表达没有显着影响。体外 BBB 的慢性 AM 治疗可能会影响这些蛋白质的定位，但不会改变蛋白质表达。

项目成果

Ueta, Y.et al.: "The gene expression in the supraoptic nucleus"Microscopy Research and Technique. 56. 158-163 (2002)

Ueta，Y.et al.：“视上核中的基因表达”显微镜研究和技术。

Date,Y.et al: "Orexins,orexinergic hypothalamic peptides,interact with automatic,neuroendocrine and neuroregulatory systems." prov Natl.Acad.sci.USA.96. 748-753 (1998)

Date，Y.et al：“食欲素，食欲素能下丘脑肽，与自动系统、神经内分泌和神经调节系统相互作用。”

山下 博.他: "脳と循環-血圧は脳によって調節される" 共立出版,東京, (1998)

Hiroshi Yamashita 等人：“大脑和循环 - 血压由大脑调节”Kyoritsu Shuppan，东京，(1998)

Kis B et al.: "Cerebral endothelium is a major source of adrenomedullin"Journal of Neuroendocrinology. (in press).

Kis B 等人：“脑内皮是肾上腺髓质素的主要来源”神经内分泌学杂志。

Serino R. et al.: "Centrally administered adrenomedullin increases Plasma oxytocin level with induction of c-fos messenger ribonucleic acid in the paraventricular and supraoptic nuclei of tha rat."Endocrinology. 140. 2334-2342 (1999)

Serino R.等人：“通过在大鼠的室旁核和视上核中诱导c-fos信使核糖核酸，集中施用肾上腺髓质素可增加血浆催产素水平。”内分泌学。