Kleinz Matthias J, Skepper Jeremy N, Davenport Anthony P
Clinical Pharmacology Unit, University of Cambridge, Level 6, Centre for Clinical Investigation, Box 110 Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK.
Regul Pept. 2005 Mar 30;126(3):233-40. doi: 10.1016/j.regpep.2004.10.019.
The novel G protein-coupled receptor APJ, recently paired with the proposed cognate peptide ligand apelin, mediates potent vasodilator and positive inotropic actions in rats. Radioligand binding showed apelin receptors in rat and human heart and human large conduit vessels. The specific cell types expressing the receptor, however, have not been determined. Apelin, the cognate receptor ligand, is present in endothelial cells. However, the exact pathway of endothelial apelin synthesis and secretion is not known. We therefore investigated the cellular distribution of APJ receptor-like immunoreactivity (APJ-LI) in a range of human tissues using immunocytochemistry and fluorescent double staining confocal microscopy. The same techniques were applied to determine the intracellular localisation of apelin-like immunoreactivity (apelin-LI) in cultured human umbilical vein endothelial cells (HUVECs). APJ-LI is present in endothelial cells, vascular smooth muscle cells and cardiomyocytes. Apelin-LI localises to secretory vesicles and the Golgi complex/endoplasmic reticulum of HUVECs. Apelin-LI does not co-localise with von Willebrand factor in Weibel-Palade bodies, suggesting synthesis of apelin via the constitutive pathway. The proximity of receptor and ligand in the human vasculature, together with evidence for local vascular apelin synthesis, suggests an important role for APJ/apelin as a paracrine cardiovascular regulator system.
新型G蛋白偶联受体APJ最近被认为与同源肽配体apelin配对，可介导大鼠体内强大的血管舒张和正性肌力作用。放射性配体结合显示大鼠和人类心脏以及人类大血管中存在apelin受体。然而，尚未确定表达该受体的具体细胞类型。同源受体配体apelin存在于内皮细胞中。然而，内皮apelin合成和分泌的确切途径尚不清楚。因此，我们使用免疫细胞化学和荧光双染共聚焦显微镜研究了一系列人类组织中APJ受体样免疫反应性（APJ-LI）的细胞分布。同样的技术被用于确定培养的人脐静脉内皮细胞（HUVECs）中apelin样免疫反应性（apelin-LI）的细胞内定位。APJ-LI存在于内皮细胞、血管平滑肌细胞和心肌细胞中。Apelin-LI定位于HUVECs的分泌囊泡和高尔基体/内质网。Apelin-LI在Weibel-Palade小体中不与血管性血友病因子共定位，提示apelin通过组成型途径合成。人类脉管系统中受体和配体的接近性，以及局部血管apelin合成的证据，提示APJ/apelin作为旁分泌心血管调节系统具有重要作用。
