The past, present and future of angiotensin II type 2 receptor stimulation

• Main Authors: U. Muscha Steckelings, Franziska Rompe, Elena Kaschina, Pawel Namsolleck, Aleksandra Grzesiak, Heiko Funke-Kaiser, Michael Bader, Thomas Unger
• Format: Article
• Language: English
• Published: Hindawi - SAGE Publishing 2010-03-01
• Series: Journal of the Renin-Angiotensin-Aldosterone System
• Online Access: https://doi.org/10.1177/1470320309347791

Studying the angiotensin type 2 receptor (AT 2 ) has been problematic in the past because a pharmacological tool for direct, specific in vitro and in vivo stimulation of the receptor has been lacking. Consequently, current knowledge about AT 2 receptor signalling and function had to be obtained by indirect approaches, like studying animals or cells with genetically altered AT 2 receptor expression levels, inhibitory experiments using specific AT 2 receptor antagonists, stimulation with angiotensin II under concomitant angiotensin II type 1 receptor blockade or stimulation with the peptide agonist CGP42112A, which has additional AT 2 receptor antagonistic properties. The recently developed non-peptide AT 2 receptor agonist Compound 21 now, for the first time, allows direct, selective and specific AT 2 receptor stimulation in vitro and in vivo . This new tool will certainly revolutionise AT 2 receptor research, enable many new insights into AT 2 receptor function and may also have the potential to become a future medical drug. This article reviews milestone findings about AT 2 receptor functional properties obtained by ‘conventional’ experimental approaches within the last 20 years. Moreover, it provides an overview of the first results obtained by direct AT 2 receptor stimulation with Compound 21, comprising effects on alkaline secretion, neurite outgrowth, blood pressure and post-infarct cardiac function.