IDENTIFICATION OF ANGIOTENSIN-II RECEPTOR SUBTYPES
IDENTIFICATION OF ANGIOTENSIN-II RECEPTOR SUBTYPES
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DOI：
10.1016/0006-291x(89)91054-1
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发表时间：
1989-11-30
影响因子：
3.1
通讯作者：
TIMMERMANS, PBMWM
中科院分区：
文献类型：
--
作者：
CHIU, AT;HERBLIN, WF;TIMMERMANS, PBMWM
我们已经证明了存在两个不同的亚型的血管紧张素II受体在大鼠肾上腺使用放射性配体结合和组织切片放射自显影。通过发现两种结构不同的非肽化合物DuP 753和EXP 655，可以鉴定出这两种亚型，这两种化合物对这两种亚型具有相互选择性。在大鼠肾上腺皮质中，DuP 753抑制了总AII结合的80%，在敏感位点上的IC 50值为2 × 104。10-8 M，而EXP 655仅取代20%。在大鼠肾上腺髓质中，EXP 655对AII结合产生90%的抑制作用，IC 50值为3.0 × 10 - 6。10-8 M，而DuP 753基本上没有活性。这两种化合物的组合完全抑制了两种组织中的AII结合。
We have demonstrated the existence of two distinct subtypes of the angiotensin II receptor in the rat adrenal gland using radioligand binding and tissue section autoradiography. The identification of the subtypes was made possible by the discovery of two structurally dissimilar, nonpeptide compounds, DuP 753 and EXP655, that show reciprocal selectivity for the two subtypes. In the rat adrenal cortex, DuP 753 inhibited 80% of the total AII binding with an IC50 value on the sensitive sites of 2 .times. 10-8 M, while EXP655 displaced only 20%. In the rat adrenal medulla, EXP655 gave 90% inhibition of AII binding with an IC50 value of 3.0 .times. 10-8 M, while DuP 753 was essentially inactive. The combination of the two compounds completely inhibited AII binding in both tissues.