Angiotensin II receptor type 1 - An update on structure, expression and pathology

Biochem Pharmacol. 2021 Oct:192:114673. doi: 10.1016/j.bcp.2021.114673. Epub 2021 Jul 9.

Abstract

The AT1 receptor, a major effector of the renin-angiotensin system, has been extensively studied in the context of cardiovascular and renal disease. Moreover, angiotensin receptor blockers, sartans, are among the most frequently prescribed drugs for the treatment of hypertension, chronic heart failure and chronic kidney disease. However, precise molecular insights into the structure of this important drug target have not been available until recently. In this context, seminal studies have now revealed exciting new insights into the structure and biased signaling of the receptor and may thus foster the development of novel therapeutic approaches to enhance the efficacy of pharmacological angiotensin receptor antagonism or to enable therapeutic induction of biased receptor activity. In this review, we will therefore highlight these and other seminal publications to summarize the current understanding of the tertiary structure, ligand binding properties and downstream signal transduction of the AT1 receptor.

Keywords: AGTR1; AT(1) receptor; AT1R; Angiotensin II; Biased agonists; Cardiovascular pathology; Protein structure; X-ray crystallography.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiotensin II / biosynthesis
  • Angiotensin II / chemistry
  • Angiotensin Receptor Antagonists / chemistry*
  • Angiotensin Receptor Antagonists / metabolism*
  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin Receptor Antagonists / therapeutic use
  • Animals
  • Gene Expression
  • Humans
  • Kidney Diseases / drug therapy
  • Kidney Diseases / metabolism
  • Protein Structure, Secondary
  • Receptor, Angiotensin, Type 1 / biosynthesis*
  • Receptor, Angiotensin, Type 1 / chemistry*
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / physiology

Substances

  • AGTR1 protein, human
  • Angiotensin Receptor Antagonists
  • Receptor, Angiotensin, Type 1
  • Angiotensin II