Co-expression of urotensin II and its receptor (GPR14) in human cardiovascular and renal tissues
Co-expression of urotensin II and its receptor (GPR14) in human cardiovascular and renal tissues
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DOI：
10.1097/00004872-200112000-00011
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发表时间：
2001-12-01
影响因子：
4.9
通讯作者：
Hirata, Y
中科院分区：
文献类型：
--
作者：
Matsushita, M;Shichiri, M;Hirata, Y
背景尿加压素-II（UII）是一种从鱼类尾垂体中分离出来的环状十二肽，具有很强的心血管作用，最近被鉴定为G蛋白偶联受体GPR 14的内源性配体。目的探讨人（h）尿苷二肽样免疫反应性（hUII-LI）在人体体液中的存在情况，方法建立了hUII和GPR 14基因的特异性放射免疫分析方法，并对hUII和GPR 14基因在人体组织中的表达进行了真实的检测。采用时间定量逆转录聚合酶链反应方法，使用LightCycler定量hUII和GPR 14 mRNA。人尿提取物的相高效液相色谱显示与已知hUII共洗脱的hUII-LI的单一主峰。正常人尿液中hUII-LI的浓度为7.4 ± 0.9 μ g/g肌酐，而其血浆浓度检测不到（< 50 pg/ml）。尿hUII浓度从原发性高血压和肾小管异常的患者，但没有肾小球疾病，显着高于正常人。由此产生的hUII的排泄分数，超过肾小球滤过率，表明尿UII-LI的肾脏起源。hUII mRNA在肾脏和右心房中大量表达，但在血管中表达较少，而GPR 14 mRNA在心血管和肾脏组织中同样大量表达。结论这些数据表明，尿hUII主要来源于肾脏，并且hUII不仅在心血管系统中起自分泌/旁分泌血管活性因子的作用，而且在肾脏中也起作用。一个尚未明确的功能。J Hypertens 19：2185-2190（C）2001 Lippincott威廉姆斯和威尔金斯。
Background Urotensin-II (UII), a cyclic dodecapeptide originally isolated from fish urophysis that has potent cardiovascular effects, has recently been identified as an endogenous ligand for the orphan G protein-coupled receptor, GPR14. The physiological roles of endogenous UII and its receptor in humans remain unknown.Objective To investigate the presence of human (h) UII-like immunoreactivity (hUII-LI) in human biological fluids, and the expression of hUII and GPR14 genes in human tissues.Methods We have established a specific radioimmunoassay for hUII and the real-time quantitative reverse transcriptase polymerase chain reaction method using LightCycler for the quantification of hUII and GPR14 mRNAs.Results Gel filtration and reverse-phase high performance liquid chromatography of human urine extracts revealed a single major peak of hUII-LI co-eluting with known hUII. The concentrations of hUII-LI in urine from normal individuals were 7.4 +/- 0.9 mug/g creatinine, whereas its plasma concentration was undetectable (< 50 pg/ml). Urinary hUII concentrations from patients with essential hypertension and those with renal tubular abnormality, but not with glomerular diseases, were significantly greater than those from normal individuals. The resulting fractional excretion of hUII, exceeding the glomerular filtration rate, suggests a renal origin of urinary UII-LI. hUII mRNAs were abundantly expressed in the kidney and the right atrium, but far less so in the vasculature, whereas GPR14 mRNAs were equally and abundantly expressed in both cardiovascular and renal tissues.Conclusions These data suggest that urinary hUII is derived mainly from a renal source, and that hUII functions as an autocrine/paracrine vasoactive factor not only in the cardiovascular system, but also in the kidney, with an as yet unspecified function. J Hypertens 19:2185-2190 (C) 2001 Lippincott Williams & Wilkins.