Endocrine Abstracts

The angiotensin II type 1 receptor (AT₁R) belongs to the family of seven trans-membrane (7TM) receptors, also referred to as G-protein coupled receptors. The AT₁R is the primary effector of the renin–angiotensin system, and serves as a key regulator of cardiovascular physiology. The importance of the receptor is clearly illustrated be the frequent use of AT₁R blockers and ACE inhibitors in cardiovascular medicine. Upon binding of Ang II the AT₁R is signals through both G protein-dependent and -independent pathways. The G protein-dependent pathways are well established and studied in detail whereas we know less about G protein-independent pathways. Pharmacological targeted activation and blocking of the signaling cascades provides novel tools to increase the understanding of how these receptors exert their cellular functions and importantly it present a new clinical potential. This so-called biased agonism (or functional selectivity) has been studied extensively for the last decade and the focus is still increasing. In this talk I will introduce the concept of AT₁R mediated biased agonism, discuss the underlying complexity of the AT₁R signaling transduction networks and gene regulation and present the clinical potential of AT₁R biased agonists.