Details

Autor(en) / Beteiligte

• Tóth, András D
• Turu, Gábor
• Hunyady, László
• Balla, András

Titel

Novel mechanisms of G-protein-coupled receptors functions: AT 1 angiotensin receptor acts as a signaling hub and focal point of receptor cross-talk

Ist Teil von

• Best practice & research. Clinical endocrinology & metabolism, 2018-04, Vol.32 (2), p.69

Ort / Verlag

Netherlands

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• AT angiotensin receptor (AT R), a prototypical G protein-coupled receptor (GPCR), is the main receptor, which mediates the effects of the renin-angiotensin system (RAS). AT 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 AT R leads to pleiotropic signal transduction pathways generating arrays of complex cellular responses. Growing amount of evidence shows that AT 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 AT 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 AT R function, signaling, regulation, dimerization or oligomerization and its cross-talk with other receptors, including epidermal growth factor (EGF) receptor, adrenergic receptors and CB cannabinoid receptor. Better understanding of the mechanisms and structural aspects of AT R activation and cross-talk can lead to the development of novel type of drugs for the treatment of cardiovascular and other diseases.