人类尿素-II是一种强大的血管收缩剂和孤儿受体GPR14的激动剂
R S Ames1, H M Sarau, J K Chambers
1Department of Molecular Biology, Smith Kline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939, USA. bobvames1@sbphrd.com
Nature
|September 28, 1999
概括
尿素-II (U-II) 是一种强大的血管收缩剂,它与心血管组织中新发现的G蛋白结合受体 (GPR14) 结合. 这种显著增加血压,并损害心脏功能,这表明更广泛的生理作用.
科学领域:
- 心血管药理学心血管药理学
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 尿素-II (U-II) 是一种类似于体静止素的循环,最初从鱼中分离出来.
- 人类U-II及其受体 (GPR14) 最近被确定,其表达主要在心血管组织中.
研究的目的:
- 为了识别和表征人类的泌尿素-II受体.
- 研究人类U-II对心血管系统的生理影响.
主要方法:
- 人类G蛋白结合受体 (GPR14) 的鉴定,同类于大鼠GPR14.
- 使用复合人体GPR14和Goby/人体U-II.II的结合试验.
- 测量调动的功能性测试.
- 从非人类灵长类动物中分离出动脉的ex vivo研究.
- 在麻醉非人类灵长类动物的体内研究.
主要成果:
- 一个人类的G蛋白结合受体 (GPR14) 被确定并确认为U-II受体.
- 人类U-II与GPR14具有高度亲和力,从而触发调动.
- 人类U-II存在于血管和心脏组织中,包括冠状动脉动脉瘤.
- U-II是一种强烈的血管收缩剂,比内甲素-1更强大.
- 在体内,U-II增加了外围耐药性,并导致灵长类动物的心脏功能障碍.
- 在中枢神经系统和内分泌组织中也检测到U-II免疫活性.
结论:
- 人类U-II通过心血管表达受体GPR14起作用.
- 人类U-II是迄今为止发现的最强大的哺乳动物血管收缩剂.
- U-II在调节血管度和心脏功能方面发挥着重要作用,在其他系统中也有潜在的作用.
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