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.

从人嗜铬细胞瘤分离出的肾上腺果蛋白（AM）是有效的降压肽之一。本研究的目的是检查AM在中枢神经系统（CNS）中的生理作用。我们已经证明大鼠脑内皮细胞会产生并分泌大量的AM体外血脑屏障（BBB）制剂。 （1）从颈vain，颈动脉和上牙后腔静脉在血浆中收集的血浆中AM的浓度如下。在颈静脉中收集了血浆中AM的最高浓度。（2）在大鼠的大鼠中进行经皮的脑脊液脑脊液（CSF）水龙头，以确定CSF中AM的浓度。用乙醚麻醉的大鼠CSF中AM的浓度比异氟烷的浓度高。 CSF中AM的浓度在饮用2％盐水期间5和7天高的3-4倍以上增加了3-4倍。（3）慢性AM暴露在体外BBB中增加了跨内皮电阻，这表明细胞间连接处的拧紧。 AM对紧密连接蛋白的表达没有显着影响（Claudin-1，occludin和ZO-1）。体外BBB的慢性AM治疗可能会影响这些蛋白质的定位而不会改变蛋白质表达。

项目成果

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。

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。”

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。

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.: "Adrenomedullin regulates blood-brain barrier functions in vitro"Neuroreport. 12. 4139-4142 (2001)

Kis B 等人：“肾上腺髓质素在体外调节血脑屏障功能”神经报告。