β-arrestin and β-adrenergic Receptor

Abstract: The Nobel Prize in Chemistry 2012 was awarded jointly to Robert J. Lefkowitz and Brian K. Kobilka “for studies of G-protein-coupled receptors”. Robert J. Lefkowitz discovered β-arrestin1 more than 20 years ago， when he studied the mechanism of β-AR (β-adrenergic receptor) desensitization， and proved that it involves in the desensitization， internalization and degradation of β-AR in his subsequent researches. More recently， new evidence has revealed the “biased agonism” of β-arrestin dependent signal pathway of β-AR， which is independent of G protein. Excitingly， this biased signaling was suggested to confer cardioprotection. In addition， β-AR blockers were discovered and widely used in the pharmacotherapy of cardiovascular diseases among many other β-AR targeted cardiovascular drugs， which was a breakthrough in the 20th century. However， most of these drugs take effect only by regulating the β-AR itself and block all of the signal pathways and functions， including both the pathological signaling and effect induced by the increased stimulation of β-AR and the normal physiological ones， which leads to some severe adverse reactions. Therefore， it will be a great progress in the treatment of cardiovascular diseases to develop the drug that can both selectively block the harmful signaling and effect and activate the beneficial physiological signaling (such as the β-arrestin signaling) of β-AR. The research and development of ligand drug for β-AR will focus on its highly selective downstream signal pathways. This article is to review the discovery of the β-arrestin and its interaction with β-AR， to offer a reference for the pharmacotherapy of cardiovascular diseases.

CSTR: 32200.14.cjcb.2012.11.0002