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Molecular Aspects of AT2 Receptor

  • Chapter
Angiotensin Vol. I

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 163 / 1))

Abstract

The octapeptide angiotensin II (Ang II) binds to two subtypes of receptors, AT1 and AT2, that both belong to the superfamily of G protein-coupled receptors (GPCRs). The AT1 subtype is a classical GPCR in terms of coupling and signaling, and appears to mediate all known physiological actions of Ang II. In contrast, the AT2 subtype is an atypical receptor that has remained a puzzle since its discovery in 1989 and molecular cloning in 1993. Over the past 10 years, a number of studies have aimed at elucidating the signaling pathways and functions of the AT2 subtype. A role for AT2 receptors has been established during fetal development and in cardiovascular, brain, and renal functions. In most cases, the AT2 receptor has been shown to counteract the effects of the AT1 subtype. AT2 also negatively cross-talks with growth factor receptors and plays a major role in the processes of apoptosis, migration, differentiation, and tissue regeneration. Depending on the cellular model and function examined, the AT2 receptor activates different signaling pathways, that can be classified into three major types: regulation of protein phosphorylation, activation of phospholipases, and/or regulation of nitric oxide (NO)/cGMP. In the present chapter, we review recent advances on the molecular aspects of the AT2 receptor: its structural features (functional domains involved in ligand binding and receptor activation), signaling pathways, coupling to G proteins and association with other intracellular partners. We then examine the molecular mechanisms by which AT2 antagonizes the effects of the AT1 subtype. Examples of AT2 receptor gene alterations associated with human diseases such as congenital anomalies of kidney and urinary tract (CAKUT) or X-linked mental retardation, are also discussed.

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Authors and Affiliations

  1. Department of Cell Biology, Institut Cochin, 22, rue Mechain, 75014, Paris, France

    C. Nahmias & C. Boden

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  1. C. Nahmias
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  2. C. Boden
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  1. Center for Cardiovascular Research (CCR) Institut für Pharmakologie und Toxikologie Charité Campus Mitte, Charité — Universitätsmedizin Berlin, Hessische Strasse 3-4, 10115, Berlin, Germany

    Thomas Unger

  2. Drug Innovation & Approval, Aventis Pharma Deutschland GmbH, Bldg. H 831, Room C 320, 65926, Frankfurt/Main, Germany

    Bernward A. Schölkens

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Nahmias, C., Boden, C. (2004). Molecular Aspects of AT2 Receptor. In: Unger, T., Schölkens, B.A. (eds) Angiotensin Vol. I. Handbook of Experimental Pharmacology, vol 163 / 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18495-6_17

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  • DOI: https://doi.org/10.1007/978-3-642-18495-6_17

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