血管紧张素 II 受体：克隆与调控

Angiotensin II receptors: cloning and regulation.

作者信息

Inagami T, Iwai N, Sasaki K, Guo D F, Furuta H, Yamano Y, Bardhan S, Chaki S, Makito N, Badr K

机构信息

Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee.

出版信息

Arzneimittelforschung. 1993 Feb;43(2A):226-8.

PMID:8498969

Abstract

Angiotensin II subtype 1 (AT1) receptor cDNA was cloned by expression cloning from bovine adrenal cortical cells. Human AT1 receptor was also cloned. These receptors were found to have a seven transmembrane structure. The receptor seems to interact with more than one type of G-proteins. AT1 consists of subtypes. cDNA for AT1A was cloned from rat kidney and that for AT1B was cloned from rat adrenal by plaque hybridization. They have similar base sequences in the coding region but are different in non-coding regions. Their functional implication is not clear. The regulation of the receptors occur at many stages. Expression of mRNA is studied in cultured rat mesangial cells. It was down regulated by angiotensin II and cAMP. On the other hand in whole body experiments, chronic infusion of angiotensin II was shown to upregulate adrenal AT1, and bilateral nephrectomy or losartan (CAS 124750-99-8) administration reduced AT1 mRNA expression. In addition to AT1 and AT2 the presence of a new subtype AT3 has been shown.

摘要

血管紧张素 II 1型（AT1）受体的互补DNA（cDNA）是通过从牛肾上腺皮质细胞进行表达克隆而获得的。人AT1受体也被克隆出来。发现这些受体具有七跨膜结构。该受体似乎与不止一种类型的G蛋白相互作用。AT1由多种亚型组成。通过噬菌斑杂交从大鼠肾脏克隆出了AT1A的cDNA，从大鼠肾上腺克隆出了AT1B的cDNA。它们在编码区具有相似的碱基序列，但在非编码区有所不同。它们的功能意义尚不清楚。受体的调节发生在多个阶段。在培养的大鼠系膜细胞中研究了mRNA的表达。它受到血管紧张素II和环磷酸腺苷（cAMP）的下调。另一方面，在整体实验中，长期输注血管紧张素II显示可上调肾上腺AT1，而双侧肾切除或给予氯沙坦（CAS 124750 - 99 - 8）可降低AT1 mRNA的表达。除了AT1和AT2之外，还显示存在一种新的亚型AT3。