ArticleThe Journal of biological chemistry2013
The arrestin-selective angiotensin AT1 receptor agonist [Sar1,Ile4,Ile8]-AngII negatively regulates bradykinin B2 receptor signaling via AT1-B2 receptor heterodimers.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
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- Molecular Effects of Auto-Antibodies on Angiotensin II Type 1 Receptor Signaling and Cell Proliferation.International journal of molecular sciences · 2022Article
- ACE2 internalization induced by a SARS-CoV-2 recombinant protein is modulated by angiotensin II type 1 and bradykinin 2 receptors.Life sciences · 2022Article
- Novel Pharmacology Following Heteromerization of the Angiotensin II Type 2 Receptor and the Bradykinin Type 2 Receptor.Frontiers in endocrinology · 2022Article
- Further comment on articles pertaining to: "Homocysteine as a potential predictor of cardiovascular risk in patients with COVID-19".Medical hypotheses · 2021Article
- Review
- Beta-Arrestins in the Treatment of Heart Failure Related to Hypertension: A Comprehensive Review.Pharmaceutics · 2021Review
- Vascular Cells Proteome Associated with Bradykinin and Leptin Inflammation and Oxidative Stress Signals.Antioxidants (Basel, Switzerland) · 2020Article
- Role of Endothelial G Protein-Coupled Receptor Kinase 2 in Angioedema.Hypertension (Dallas, Tex. : 1979) · 2020Article
- Angiotensin ATJournal of neuroinflammation · 2020Article
- Angiotensin Receptors Heterodimerization and Trafficking: How Much Do They Influence Their Biological Function?Frontiers in pharmacology · 2020Review
- Arrestin recruitment and signaling by G protein-coupled receptor heteromers.Neuropharmacology · 2019Review
- The ATRQβ-001 vaccine improves cardiac function and prevents postinfarction cardiac remodeling in mice.Hypertension research : official journal of the Japanese Society of Hypertension · 2019Article
- The Role of β-Arrestin Proteins in Organization of Signaling and Regulation of the AT1 Angiotensin Receptor.Frontiers in endocrinology · 2019Review
- Discovery of Pathologic GPCR Aggregation.Frontiers in medicine · 2019Review
- Commentary: Central-acting therapeutics alleviate respiratory weakness caused by heart failure-induced ventilatory overdrive.Frontiers in physiology · 2018Article
- Current topics in angiotensin II type 1 receptor research: Focus on inverse agonism, receptor dimerization and biased agonism.Pharmacological research · 2017Review
- S1P in HDL promotes interaction between SR-BI and S1PR1 and activates S1PR1-mediated biological functions: calcium flux and S1PR1 internalization.Journal of lipid research · 2017Article
- The conformational signature of β-arrestin2 predicts its trafficking and signalling functions.Nature · 2016Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The renin-angiotensin and kallikrein-kinin systems are key regulators of vascular tone and inflammation. Angiotensin II, the principal effector of the renin-angiotensin system, promotes vasoconstriction by activating angiotensin AT1 receptors. The opposing effects of the kallikrein-kinin system are mediated by bradykinin acting on B1 and B2 bradykinin receptors. The renin-angiotensin and kallikrein-kinin systems engage in cross-talk at multiple levels, including the formation of AT1-B2 receptor heterodimers. In primary vascular smooth muscle cells, we find that the arrestin pathway-selective AT1 agonist, [Sar(1),Ile(4),Ile(8)]-AngII, but not the neutral AT1 antagonist, losartan, inhibits endogenous B2 receptor signaling. In a transfected HEK293 cell model that recapitulates this effect, we find that the actions of [Sar(1),Ile(4), Ile(8)]-AngII require the AT1 receptor and result from arrestin-dependent co-internalization of AT1-B2 heterodimers. BRET50 measurements indicate that AT1 and B2 receptors efficiently heterodimerize. In cells expressing both receptors, pretreatment with [Sar(1),Ile(4),Ile(8)]-AngII blunts B2 receptor activation of Gq/11-dependent intracellular calcium influx and Gi/o-dependent inhibition of adenylyl cyclase. In contrast, [Sar(1),Ile(4),Ile(8)]-AngII has no effect on B2 receptor ligand affinity or bradykinin-induced arrestin3 recruitment. Both radioligand binding assays and quantitative microscopy-based analysis demonstrate that [Sar(1),Ile(4),Ile(8)]-AngII promotes internalization of AT1-B2 heterodimers. Thus, [Sar(1),Ile(4),Ile(8)]-AngII exerts lateral allosteric modulation of B2 receptor signaling by binding to the orthosteric ligand binding site of the AT1 receptor and promoting co-sequestration of AT1-B2 heterodimers. Given the opposing roles of the renin-angiotensin and kallikrein-kinin systems in vivo, the distinct properties of arrestin pathway-selective and neutral AT1 receptor ligands may translate into different pharmacologic actions.
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