Molecular cloning of AT1 angiotensin receptors.
Molecular cloning of AT1 angiotensin receptors.
复制标题
AT1 血管紧张素受体的分子克隆。
DOI：
10.1093/ajh/5.12.236s
复制
发表时间：
1992
影响因子：
3.2
通讯作者：
Alexander,RW
中科院分区：
文献类型：
--
作者：
Murphy,TJ;Takeuchi,K;Alexander,RW
血管紧张素II是肾素-血管紧张素系统的主要效应分子。它的作用是由被称为AT受体的细胞表面蛋白介导的。在放射性配基结合研究的基础上，从药理学角度将其分为AT1受体和AT2结合位点两大类(邱阿特等，Biochem BiPhys res Commun；165：196-203)。AT1受体似乎介导了血管紧张素II的主要心血管效应，但尚无已知的生理特性与AT2结合位点偶联(Wong PC等，J Pharmacol Exp Ther 1990；255：584-592)。为了进一步了解AT1受体的功能，我们分离了大鼠编码两种不同但高度相似的AT1受体亚型的基因，称为AT1a和AT1b受体。采用表达克隆的方法，从血管平滑肌细胞的cDNA文库中分离到两个编码血管AT1a受体的基因。用这种方法分离的克隆的特性与已知的AT1受体的药理、生化信号和组织分布特性是一致的。以此为探针，从基因组文库中分离到大鼠AT1受体的第二个亚型。这种受体被称为AT1b受体，氨基酸序列95%相同，在药理上与AT1a受体没有区别。然而，AT1b基因的组织特异性表达模式与AT1a受体的组织特异性表达模式显著不同。Am J Hyperten 1992；5：236S-242S
Angiotensin II is the principal effector molecule of the renin-angiotensin system. Its effects are mediated by cell surface proteins termed AT receptors. On the basis of radioligand binding studies, these have been pharmacologically subdivided into two classes, termed AT1receptors and AT2binding sites (Chiu AT, et al, Biochem Biophys Res Commun 1989;165:196–203). AT1receptors appear to mediate the major cardiovascular effects of angiotensin II, whereas no known physiological properties appear to be coupled to AT2binding sites (Wong PC, et al, J Pharmacol Exp Ther 1990;255:584-592). To gain further insight into the function of AT1receptors we have isolated rat cDNA’s and genes encoding two distinct but highly similar isoforms of AT1receptors, termed AT1aand AT1breceptors. Two cDNA’s encoding the vascular AT1areceptor were isolated by an expression cloning strategy from a cDNA library prepared from vascular smooth muscle cells. The properties of the clones isolated by this approach are consistent with known pharmacological, biochemical signaling, and tissue distribution properties of AT1receptors. Using this cDNA as a probe, a second isoform of rat AT1receptor was isolated from a genomic library. This receptor, termed the AT1breceptor, is 95% identical in amino acid sequence and is pharmacologically indistinguishable from the AT1areceptor. However, the tissue-specific expression pattern of the AT1bgene differs significantly from that for the AT1areceptor. Am J Hypertens 1992;5:236S–242S