Impairment of agonist-induced M2 muscarinic receptor activation by autoantibodies from chagasic patients with cardiovascular dysautonomia

Impairment of agonist-induced M2 muscarinic receptor activation by autoantibodies from chagasic patients with cardiovascular dysautonomia

Copyright © 2020 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 212(2020) vom: 01. März, Seite 108346
1. Verfasser: Beltrame, Sabrina P (VerfasserIn)
Weitere Verfasser: Carrera Páez, Laura C, Auger, Sergio R, Sabra, Ahmad H, Bilder, Claudio R, Waldner, Claudia I, Goin, Juan C
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2020
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Autoantibodies Chagas Dysautonomia Muscarinic receptors Cholinergic Agonists Receptor, Muscarinic M2 beta-Arrestin 1 Carbachol mehr... 8Y164V895Y GTP-Binding Protein alpha Subunits, Gi-Go EC 3.6.5.1 GTP-Binding Protein alpha Subunits, Gq-G11
Beschreibung
Zusammenfassung:Copyright © 2020 Elsevier Inc. All rights reserved.
Previous studies showed that circulating autoantibodies against M2 muscarinic receptors (anti-M2R Ab) are associated with decreased cardiac parasympathetic modulation in patients with chronic Chagas disease (CD). Here we investigated whether the exposure of M2R to such antibodies could impair agonist-induced receptor activation, leading to the inhibition of associated signaling pathways. Preincubation of M2R-expressing HEK 293T cells with serum IgG fractions from chagasic patients with cardiovascular dysautonomia, followed by the addition of carbachol, resulted in the attenuation of agonist-induced Gi protein activation and arrestin-2 recruitment. These effects were not mimicked by the corresponding Fab fractions, suggesting that they occur through receptor crosslinking. IgG autoantibodies did not enhance M2R/arrestin interaction or promote M2R internalization, suggesting that their inhibitory effects are not likely a result of short-term receptor regulation. Rather, these immunoglobulins could function as negative allosteric modulators of acetylcholine-mediated responses, thereby contributing to the development of parasympathetic dysfunction in patients with CD
Beschreibung:Date Completed 19.10.2020
Date Revised 19.10.2020
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2020.108346