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Structural Features Influencing the Bioactive Conformation of Angiotensin II and Angiotensin A: Relationship between Receptor Desensitization, Addiction, and the Blood-Brain Barrier.
Int J Mol Sci
May 2024
Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada.
The N-terminal portion of the octapeptide angiotensin II (DRVYIHPF; AngII), a vasopressor peptide that favorably binds to, and activates, AngII type 1 receptor (ATR), has an important role in maintaining bioactive conformation. It involves all three charged groups, namely (i) the N-terminal amino group cation, (ii) the Asp sidechain anion and (iii) the Arg guanidino cation. Neutralization of any one of these three charged groups results in a substantial reduction (<5%) in bioactivity, implicating a specialized function for this cluster.
View Article and Find Full Text PDFAngiotensin II Type 1 Receptor Tachyphylaxis Is Defined by Agonist Residence Time.
Hypertension
January 2022
Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil (D.A.D., L.T.P.-e.-S., E.B.O., C.M.C.-N.).
Several GPCRs (G-protein-coupled receptors) have been reported to exhibit tachyphylaxis, which is an acute loss of functional receptor response after repeated stimuli with an agonist. GPCRs are important clinical targets for a wide range of disorders. Therefore, elucidation of the ligand features that contribute to receptor tachyphylaxis and signaling events underlying this phenomenon is important for drug discovery and development.
View Article and Find Full Text PDFAngiotensin II-Induced Cardiac Effects Are Modulated by Endocannabinoid-Mediated CB Receptor Activation.
Cells
March 2021
Department of Physiology, Semmelweis University, 1094 Budapest, Hungary.
Angiotensin II (Ang II) has various cardiac effects and causes vasoconstriction. Ang II activates the type-1 angiotensin receptor-G signaling pathway resulting in the release of 2-arachidonoylglycerol (2-AG). We aimed to investigate whether cardiac Ang II effects are modulated by 2-AG-release and to identify the role of type-1 cannabinoid receptors (CBR) in these effects.
View Article and Find Full Text PDFFast relaxation and desensitization of angiotensin II contraction in the pulmonary artery via AT1R and Akt-mediated phosphorylation of muscular eNOS.
Pflugers Arch
October 2019
Department of Physiology, Seoul National University College of Medicine, Seoul, 03080, South Korea.
Angiotensin II (AngII) triggers a transient contraction of pulmonary arteries (PAs) followed by protracted desensitization. Based on the unconventional eNOS expression in PA smooth muscle cells (PASMCs), we hypothesized that activation of smooth muscle eNOS by AngII might be responsible for fast relaxation and tachyphylaxis. Using dual-wire myograph, mechanically endothelium-denuded rat PA [E(-)PA] showed AngII concentration-dependent transient contractions (ΔT, 95% decay within 1 min), which were abolished by losartan (AT1R antagonist).
View Article and Find Full Text PDFAlterations in vascular function by syncytiotrophoblast extracellular vesicles via lectin-like oxidized low-density lipoprotein receptor-1 in mouse uterine arteries.
Clin Sci (Lond)
November 2018
Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Canada
Syncytiotrophoblast extracellular vesicles (STBEVs), released into the maternal circulation during pregnancy, have been shown to affect vascular function; however, the mechanism remains unknown. In rats, STBEVs were shown to reduce endothelium-mediated vasodilation via lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a multi-ligand scavenger receptor that has been associated with vascular dysfunction. Recently, LOX-1 was shown to interact with the angiotensin II type 1 receptor (AT-1).
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