From angiotensin IV binding site to AT4 receptor

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 AT1 and/or AT2 receptors. Moreover the discovery of high affinity [125I]-Ang IV binding sites and their particular tissue distribution led to the concept of the AT4 receptor. An important breakthrough was achieved by defining the AT4 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 AT4 receptor by providing an overview of the cellular effects by AT4 ligands.