Ames R S, Sarau H M, Chambers J K, Willette R N, Aiyar N V, Romanic A M, Louden C S, Foley J J, Sauermelch C F, Coatney R W, Ao Z, Disa J, Holmes S D, Stadel J M, Martin J D, Liu W S, Glover G I, Wilson S, McNulty D E, Ellis C E, Elshourbagy N A, Shabon U, Trill J J, Hay D W, Ohlstein E H, Bergsma D J, Douglas S A
Department of Molecular Biology, Smith Kline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939, USA.
Nature. 1999 Sep 16;401(6750):282-6. doi: 10.1038/45809.
Urotensin-II (U-II) is a vasoactive 'somatostatin-like' cyclic peptide which was originally isolated from fish spinal cords, and which has recently been cloned from man. Here we describe the identification of an orphan human G-protein-coupled receptor homologous to rat GPR14 and expressed predominantly in cardiovascular tissue, which functions as a U-II receptor. Goby and human U-II bind to recombinant human GPR14 with high affinity, and the binding is functionally coupled to calcium mobilization. Human U-II is found within both vascular and cardiac tissue (including coronary atheroma) and effectively constricts isolated arteries from non-human primates. The potency of vasoconstriction of U-II is an order of magnitude greater than that of endothelin-1, making human U-II the most potent mammalian vasoconstrictor identified so far. In vivo, human U-II markedly increases total peripheral resistance in anaesthetized non-human primates, a response associated with profound cardiac contractile dysfunction. Furthermore, as U-II immunoreactivity is also found within central nervous system and endocrine tissues, it may have additional activities.
尾加压素 II（U-II）是一种血管活性的“类生长抑素”环肽，最初从鱼脊髓中分离出来，最近已从人类身上克隆得到。在此我们描述了一种与大鼠GPR14同源、主要在心血管组织中表达的孤儿人类G蛋白偶联受体的鉴定，该受体作为U-II受体发挥作用。虾虎鱼和人类的U-II以高亲和力结合重组人GPR14，且这种结合在功能上与钙动员相关。在血管和心脏组织（包括冠状动脉粥样瘤）中均发现了人类U-II，并且它能有效收缩非人类灵长类动物的离体动脉。U-II的血管收缩效力比内皮素-1高一个数量级，这使得人类U-II成为迄今已鉴定出的最有效的哺乳动物血管收缩剂。在体内，人类U-II能显著增加麻醉的非人类灵长类动物的总外周阻力，这种反应与严重的心脏收缩功能障碍相关。此外，由于在中枢神经系统和内分泌组织中也发现了U-II免疫反应性，它可能还具有其他活性。
