Immunolocalizations of ET-1, ET receptors and CGRP in endothelial cells

血管内皮细胞通过产生内皮素（ET）-1和降钙素基因相关肽（CGRP）等血管活性肽，并将其释放到血管腔和内皮下层，在局部血流调节中发挥重要作用。免疫电镜观察显示，ET-1和CGRP在大鼠硬脑膜横静脉窦和颈动脉体内皮细胞的粗面内质网-高尔基体系统中合成和分离，部分储存在韦贝尔-帕拉德（WP）小体中。EP-1通过调节胞吐作用释放到血管腔和内皮下层，EP-1通过旁分泌方式引起内侧肌细胞膜上ETA受体介导的血管收缩，通过自分泌方式引起内皮细胞膜上ETB受体介导的血管舒张。免疫细胞化学结果显示，ETB受体定位于横静脉窦内皮细胞和颈动脉体的质膜，ETA受体定位于横静脉窦内侧肌细胞的肌膜。在颈动脉体的动脉系统中，未检测到ETA受体的免疫反应。这些发现表明，ET-1通过诱导ETA受体介导的血管收缩和ETB受体介导的血管舒张来调节横窦中的血流，并且ET-1通过唤起ETB受体介导的血管舒张来保持通过颈动脉体的大量血流。

Vascular endothelial cells play the improtant roles in regulation of the local blood flow by producing some vasoactive peptides such as endothelin (ET) -1 and calcitonin gene-related peptide (CGRP), and by releasing them into both vascular lumen and subendothelial layr. Our immunoelectron microscopy revealed that ET-1 and CGRP are synthesized and segregated in the rough endoplasmic reticulum-Golgi system, stored in part in Weibel-Palade (WP) bodies in endothelial cells of the transverse venous sinus of the rat dura mater and the artery of the rat carotid body. In addition, we confirmed that both peptides are extracellularly released from the WP bodies into both vascular lumen and subendothelial layr by exocytosis in a manner of regulated pathway.It is widely accepted that EP-1 induces vasoconstriction mediated from ETA receptors on the sarcolemma of medial muscle cells in a manner of paracrine, and vasodilatation mediated from ETB receptors on the plasmalemma of endothelial cells in a manner of autocrine. The present immunocytochemisty showed that immunoreactivities of the ETB receptors are localized to the plasmalemma of endothelial cells of the transverse venous sinus and the artery in the carotid body, and that those of ETA receptors are localized to the sarcolemma of medial muscle cells of the transverse venous sinus. In the arterial system of the carotid body, we could not detect out immunoreactions of the ETA receptors. These findings suggest that ET-1 regulates the blood flow in the transverse sinus by inducing both vasocontraction mediated from ETA receptors and vasodilatation mediated from ETB receptors, and that ET-1 preserves an abundance of the blood flow through the carotid body by evoking the vasodilatation mediated from ETB receptors.