Biased agonism/antagonism at the AngII-AT1 receptor: Implications for adrenal aldosterone production and cardiovascular therapy

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
Jennifer ManingAnastasios Lymperopoulos

Abstract

Many of the effects of angiotensin II (AngII), including adrenocortical aldosterone release, are mediated by the AngII type 1 receptor (AT1R), a receptor with essential roles in cardiovascular homeostasis. AT1R belongs to the G protein-coupled receptor (GPCR) superfamily, mainly coupling to the Gq/11 type of G proteins. However, it also signals through βarrestins, oftentimes in parallel to eliciting G protein-dependent signaling. This has spurred infinite possibilities for cardiovascular pharmacology, since various beneficial effects are purportedly exerted by AT1R via βarrestins, unlike AT1R-induced G protein-mediated pathways that usually result in damaging cardiovascular effects, including hypertension and aldosterone elevation. Over the past decade however, a number of studies from our group and others have suggested that AT1R-induced βarrestin signaling can also be damaging for the heart, similarly to the G protein-dependent one, with regard to aldosterone regulation. Additionally, AT1R-induced βarrestin signaling in astrocytes from certain areas of the brain may also play a significant role in central regulation of blood pressure and hypertension pathogenesis. These findings have provided the impetus for testing available...Continue Reading

Citations

Mar 28, 2019·Pharmacological Reviews·Terry Kenakin
Apr 10, 2019·International Journal of Molecular Sciences·Elena De AngelisAda Popolo
Aug 28, 2020·Frontiers in Pharmacology·Natalia L Rukavina MikusicMariela M Gironacci
Aug 14, 2019·Therapeutic Advances in Cardiovascular Disease·Uma MarkanAnastasios Lymperopoulos
Mar 14, 2020·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·Lucie S MeyerTracy Ann Williams
Aug 8, 2021·International Journal of Molecular Sciences·Samantha L CooperJeanette Woolard

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