Artículo
Interaction between the angiotensin-(1–7) mas receptor and the dopamine D2 receptor
Rukavina Mikusic, Natalia Lucía
; Silva, Mauro Gastón; Mazzitelli, Luciana Romina
; Santos, Robson A.S.; Gomez, Karina Andrea
; Grecco, Hernan Edgardo
; Gironacci, Mariela Mercedes
Fecha de publicación:
05/05/2021
Editorial:
Lippincott Williams
Revista:
Hypertension
ISSN:
0194-911X
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Ang (angiotensin) 1-7 MasR (Mas receptor) and D2R (dopamine D2 receptor) stimulation is coupled to anti-inflammatory responses. In the present work, we investigated the hypothesis that the anti-inflammatory action mediated by both receptors results from MasR-D2R heteromerization. Human monocyte (THP-1) cells differentiated to macrophages and exposed to lipopolysaccharide were employed. Ang (1-7) and the D2R agonist SUM (sumanirole) induced a decrease in proinflammatory IL (interleukin) 6 release in human macrophages exposed to a proinflammatory stimulus. The Ang (1-7)-induced decrease in IL-6 was blocked by the D2R antagonist. Conversely, the SUM induced decrease in IL-6 was prevented by the MasR antagonist and when MasR expression was downregulated, suggesting MasR-D2R interaction. Co-immunoprecipitation assay in THP-1 cells and in human monocyte differentiated macrophages from peripheral blood mononuclear cells confirmed MasR-D2R interaction. To avoid the influence from other receptors, MasR-D2R interaction was characterized in transfected human embryonic kidney 293T cells. Fluorescence resonance energy transfer analysis showed that MasR and D2R formed a constitutive heteromer, which was not modified by their agonists. Ang (1-7) and dopamine stimulated ERK (extracellular signal-regulated kinase) 1/2 and Akt (protein kinase B) phosphorylation only in cells expressing MasR-D2R heteromers, but not in cells expressing each receptor alone. Ang (1-7)-stimulated ERK1/2 and Akt phosphorylation was prevented by D2R blockade while the effect of dopamine was prevented by MasR blockade, reinforcing the fact that MasR-D2R heteromers are involved in ERK1/2 and Akt activation induced by their agonists. Our findings provide new evidence regarding the mechanisms underlying the cross-talk between the Ang (1-7)/MasR axis and the dopaminergic system in response to a proinflammatory process.
Palabras clave:
ANGIOTENSINS
,
DOPAMINE
,
LIPOPOLYSACCHARIDE
,
MACROPHAGES
,
MONOCYTE
,
PHOSPHORYLATION
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(IFIBA)
Articulos de INST.DE FISICA DE BUENOS AIRES
Articulos de INST.DE FISICA DE BUENOS AIRES
Articulos(INGEBI)
Articulos de INST.DE INVEST.EN ING.GENETICA Y BIOL.MOLECULAR "DR. HECTOR N TORRES"
Articulos de INST.DE INVEST.EN ING.GENETICA Y BIOL.MOLECULAR "DR. HECTOR N TORRES"
Articulos(IQUIFIB)
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Citación
Rukavina Mikusic, Natalia Lucía; Silva, Mauro Gastón; Mazzitelli, Luciana Romina; Santos, Robson A.S.; Gomez, Karina Andrea; et al.; Interaction between the angiotensin-(1–7) mas receptor and the dopamine D2 receptor; Lippincott Williams; Hypertension; 77; 5; 5-5-2021; 1659-1669
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