Novel mechanisms of G-protein-coupled receptors functions: AT1 angiotensin receptor acts as a signaling hub and focal point of receptor cross-talk. Issue 2 (April 2018)

• Record Type: Journal Article
• Authors: Tóth, András D.; Turu, Gábor; Hunyady, László; Balla, András
• Is Part Of: Best practice & research. Volume 32:Issue 2(2018)
• Page Start: 69
• Page End: 82
• Publication Date: 2018-04
• Subjects: GPCR -- angiotensin II -- receptor cross-talk -- bias -- dimerization; α2CAR α2C adrenergic receptor -- AngII angiotensin II -- AT1R AT1 angiotensin receptor -- β2AR β2-adrenergic receptor -- EGFR epidermal growth factor receptor -- GPCR G protein-coupled receptors -- HB–EGF heparin-binding epidermal growth factor-like growth factor -- RAS renin–angiotensin system -- VSMC vascular smooth muscle cell; Endocrine glands -- Diseases -- Periodicals; Metabolism -- Disorders -- Periodicals; Endocrinology -- Periodicals; Metabolism -- Periodicals; 616.4
• DOI: 10.1016/j.beem.2018.02.003
• Languages: English
• ISSNs: 1521-690X

Abstract

Abstract : AT1 angiotensin receptor (AT1 R), a prototypical G protein-coupled receptor (GPCR), is the main receptor, which mediates the effects of the renin-angiotensin system (RAS). AT1 R plays a crucial role in the regulation of blood pressure and salt-water homeostasis, and in the development of pathological conditions, such as hypertension, heart failure, cardiovascular remodeling, renal fibrosis, inflammation, and metabolic disorders. Stimulation of AT1 R leads to pleiotropic signal transduction pathways generating arrays of complex cellular responses. Growing amount of evidence shows that AT1 R is a versatile GPCR, which has multiple unique faces with distinct conformations and signaling properties providing new opportunities for functionally selective pharmacological targeting of the receptor. Biased ligands of AT1 R have been developed to selectively activate the β-arrestin pathway, which may have therapeutic benefits compared to the conventional angiotensin converting enzyme inhibitors and angiotensin receptor blockers. In this review, we provide a summary about the most recent findings and novel aspects of the AT1 R function, signaling, regulation, dimerization or oligomerization and its cross-talk with other receptors, including epidermal growth factor (EGF) receptor, adrenergic receptors and CB1 cannabinoid receptor. Better understanding of the mechanisms and structural aspects of AT1 R activation and cross-talk can lead to the development of novel type of drugs for the treatment of cardiovascular and other diseases.