Details

Autor(en) / Beteiligte

• Tóth, András D
• Gyombolai, Pál
• Szalai, Bence
• Várnai, Péter
• Turu, Gábor
• Hunyady, László

Titel

Angiotensin type 1A receptor regulates β-arrestin binding of the β 2 -adrenergic receptor via heterodimerization

Ist Teil von

• Molecular and cellular endocrinology, 2017-02, Vol.442, p.113

Ort / Verlag

Ireland

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• Heterodimerization between angiotensin type 1A receptor (AT R) and β -adrenergic receptor (β AR) has been shown to modulate G protein-mediated effects of these receptors. Activation of G protein-coupled receptors (GPCRs) leads to β-arrestin binding, desensitization, internalization and G protein-independent signaling of GPCRs. Our aim was to study the effect of heterodimerization on β-arrestin coupling. We found that β-arrestin binding of β AR is affected by activation of AT Rs. Costimulation with angiotensin II and isoproterenol markedly enhanced the interaction between β AR and β-arrestins, by prolonging the lifespan of β AR-induced β-arrestin2 clusters at the plasma membrane. While candesartan, a conventional AT R antagonist, had no effect on the β-arrestin2 binding to β AR, TRV120023, a β-arrestin biased agonist, enhanced the interaction. These findings reveal a new crosstalk mechanism between AT R and β AR, and suggest that enhanced β-arrestin2 binding to β AR can contribute to the pharmacological effects of biased AT R agonists.