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

肾上腺髓质素(adrenomedullin，AM)是从人嗜铬细胞瘤中分离出来的一种强降压肽。本研究旨在探讨AM在中枢神经系统(CNS)中的生理作用。我们在体外血脑屏障(BBB)制备中证实了大鼠脑内皮细胞产生和分泌大量AM。本研究结果如下：(1)测定了戊巴比妥钠麻醉大鼠颈静脉、颈动脉和肾上后腔静脉血浆中AM的浓度。采集大鼠颈静脉血中AM的浓度最高。(2)经皮脑脊液抽吸测定脑脊液中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%生理盐水的第5天和第7天，脑脊液中AM的浓度比对照组增加了3-4倍以上。(3)慢性AM暴露增加了体外血脑屏障的跨内皮细胞电阻，提示细胞间连接紧密。AM对紧密连接蛋白(claudin-1、occludin和ZO-1)的表达无明显影响。体外慢性AM处理BBB可能会影响这些蛋白的定位，但不会改变蛋白表达。

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.