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Storage and Release of Endothelin in Vascular Endothelial Cells

血管内皮细胞内皮素的储存和释放

基本信息

批准号：
05670035
负责人：
FUJIMOTO Sunao
金额：
$ 1.22万
依托单位：
University of Occupational and Environmental Health
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

Endothelin-1 (ET-1) is a potent vasoconstrictive peptide produced by vascular endothelial cells. Our immunoelectron microscopy reveals that ET-1, synthesized and segregated in the rER-Golgi system, is stored in Weibel-Palade (WP) bodies and that the processing of big ET-1 to ET-1 occurs in part in WP bodies since immunolocalizations of big ET-1 is preferentially found on the limiting membrane and those of ET-1 is in the center of WP bodies. This means that the conversion of big ET-1 segregated from the Golgi complex and stored in WP bodies to ET-1 may in part occur at the limiting membrane of WP bodies. Further studies using the double immunolabeling technique are now in progress.WP bodies of endothelial cells of the transverse sinus of the rat dura mater are immunoreactive for ET-1. The immunoreactivities are also observed in the sarcolemma and caveoles of smooth muscle cells under the endothelium. This indicates hemodynamic roles of ET-1 in the intracranial venous circulation.In addition to ET-1, WP bodies are a storage site of CGRP,a vasodilatative peptide in the rat carotid body artery derived. By the immunoelectron microscopy using the double immunolabeling technique, immunolabelings of both peptides are preferentially colocalized in the same WP bodies in a single section. The carotid body possesses the peculiar arterial microcirculatory system which may be related to efficiencies of chemoreceptor function. The existence of both vasoconstrictive and vasodilative peptides in WP bodies of the endothelial cells suggests that these peptides play important roles in local regulation of the blood flow in the carotid body.

内皮素-1(ET-1)是一种由血管内皮细胞产生的强效缩血管多肽。我们的免疫电子显微镜显示，在Rer-Golgi系统中合成和分离的ET-1储存在Webel-Palade(WP)小体中，WP小体中部分发生了大ET-1向ET-1的加工，这是因为大ET-1的免疫定位优先发现在WP小体的界限膜上，而ET-1的免疫定位在WP小体的中心。这意味着，从高尔基复合体中分离出来并储存在WP小体中的大ET-1向ET-1的转化可能部分发生在WP小体的极限膜上。使用双重免疫标记技术的进一步研究目前正在进行中。大鼠硬脑膜横窦内皮细胞的可湿性小体为ET-1免疫阳性。在内皮下的平滑肌细胞的肌膜和空洞中也观察到免疫反应。这表明ET-1在颅内静脉循环中的血流动力学作用。除了ET-1，WP小体也是CGRP的储存部位，CGRP是大鼠颈动脉体动脉中的一种血管扩张肽。采用双重免疫标记技术的免疫电子显微镜显示，两种多肽的免疫标记在同一切片中优先共存于同一WP小体中。颈动脉小体具有独特的动脉微循环系统，这可能与化学感受器功能的效率有关。内皮细胞WP小体中既有收缩血管的多肽，也有扩张血管的多肽，提示这些多肽在颈动脉小体的局部血流调节中起重要作用。