Artículo
Impairment of agonist-induced M2 muscarinic receptor activation by autoantibodies from chagasic patients with cardiovascular dysautonomia
Beltrame, Sabrina Paola
; Carrera Paez, Laura Camila
; Auger, Sergio Ricardo; Sabra, Ahmad H.; Bilder, Claudio Rubén; Waldner, Claudia Ines
; Goin, Juan Carlos
![Icon](/themes/CONICETDigital/images/conicet.png)
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Fecha de publicación:
03/2020
Editorial:
Academic Press Inc Elsevier Science
Revista:
Clinical Immunology
ISSN:
1521-6616
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
MUSCARINIC RECEPTORS
,
AUTOANTIBODIES
,
CHAGAS
,
DYSAUTONOMIA
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(CEFYBO)
Articulos de CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Articulos de CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Citación
Beltrame, Sabrina Paola; Carrera Paez, Laura Camila; Auger, Sergio Ricardo; Sabra, Ahmad H.; Bilder, Claudio Rubén; et al.; Impairment of agonist-induced M2 muscarinic receptor activation by autoantibodies from chagasic patients with cardiovascular dysautonomia; Academic Press Inc Elsevier Science; Clinical Immunology; 212; 3-2020; 1-9
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