尿紧张素抑制剂在表达重组尿紧张素II受体的细胞中模拟尿紧张素II诱导的钙释放。

Urantide mimics urotensin-II induced calcium release in cells expressing recombinant UT receptors.

作者信息

Camarda Valeria, Song Wei, Marzola Erika, Spagnol Martina, Guerrini Remo, Salvadori Severo, Regoli Domenico, Thompson Jonathan P, Rowbotham David J, Behm David J, Douglas Stephen A, Calo' Girolamo, Lambert David G

机构信息

Department of Experimental and Clinical Medicine, Section of Pharmacology, University of Ferrara, via Fossato di Mortara, 19, 44100 Ferrara, Italy.

出版信息

Eur J Pharmacol. 2004 Sep 13;498(1-3):83-6. doi: 10.1016/j.ejphar.2004.07.089.

DOI:10.1016/j.ejphar.2004.07.089

PMID:15363979

Abstract

Urotensin-II is the natural ligand of the UT receptor. This novel system is involved in the regulation of cardiovascular functions. Recently, a urotensin-II analog ([Pen5,DTrp7,Orn8]urotensin-II(4-11)) named urantide, has been proposed as a selective and potent UT receptor antagonist. In order to pharmacologically characterize this new compound, urantide was tested on the native UT receptors of the rat aorta and on the human recombinant receptors expressed in CHO cells (CHO(hUT)). Indeed, urantide behaves as a competitive, potent (pA2 8.24), and pure antagonist in the rat aorta bioassay, while as an agonist (pEC50 8.11) in a calcium mobilization assay performed in CHO(hUT) cells. Urantide should be considered a low efficacy partial agonist.

摘要

尾加压素II是UT受体的天然配体。这个新系统参与心血管功能的调节。最近，一种名为urantide的尾加压素II类似物（[Pen5，DTrp7，Orn8]尾加压素II(4 - 11)）被提议作为一种选择性强效UT受体拮抗剂。为了从药理学上表征这种新化合物，对urantide在大鼠主动脉的天然UT受体以及在CHO细胞（CHO(hUT)）中表达的人重组受体上进行了测试。实际上，在大鼠主动脉生物测定中，urantide表现为竞争性、强效（pA2 8.24）的纯拮抗剂，而在CHO(hUT)细胞中进行的钙动员测定中则表现为激动剂（pEC50 8.11）。Urantide应被视为低效能部分激动剂。