Vanderheyden Patrick M L
Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Brussels, Belgium.
Mol Cell Endocrinol. 2009 Apr 29;302(2):159-66. doi: 10.1016/j.mce.2008.11.015. Epub 2008 Nov 21.
One of the fragments of the cardiovascular hormone Angiotensin II incited the interest of several research groups. This 3-8 fragment, denoted as Angiotensin IV (Ang IV) causes a number of distinct biological effects (see Introduction), unlikely to be explained by its weak binding to AT(1) and/or AT(2) receptors. Moreover the discovery of high affinity [(125)I]-Ang IV binding sites and their particular tissue distribution led to the concept of the AT(4) receptor. An important breakthrough was achieved by defining the AT(4) receptor as the membrane-bound insulin-regulated aminopeptidase (IRAP). Crucial for the definition as a receptor the binding of the endogenous ligand(s) should be linked to particular cellular and/or biochemical processes. With this respect, cultured cells offer the possibility to study the presence of binding sites in conjunction with ligand induced signaling. This link is discussed for the AT(4) receptor by providing an overview of the cellular effects by AT(4) ligands.
心血管激素血管紧张素II的一个片段引起了多个研究小组的兴趣。这个3 - 8片段，被称为血管紧张素IV（Ang IV），会引发许多不同的生物学效应（见引言），不太可能通过其与AT(1)和/或AT(2)受体的弱结合来解释。此外，高亲和力[(125)I]-Ang IV结合位点的发现及其特殊的组织分布引出了AT(4)受体的概念。将AT(4)受体定义为膜结合的胰岛素调节氨肽酶（IRAP）取得了一项重要突破。对于定义为受体而言至关重要的是，内源性配体的结合应与特定的细胞和/或生化过程相关联。在这方面，培养细胞提供了结合配体诱导信号研究结合位点存在情况的可能性。通过概述AT(4)配体的细胞效应来讨论AT(4)受体的这种关联。
