Fig. 4.

Recruitment of β-arrestin-2 with TRV120023 with no activation of G-protein-mediated signaling. A: dose response of TRV120023 in human embryonic kidney (HEK)293 cells overexpressing ANG II type 1 receptor (AT1R) for recruitment of β-arrestin and activation of G-protein [inositol monophosphate 1 (IP-One)] reveals selective recruitment of β-arrestin. Data are mean ± SE for 15–20 independent experiments. B: dose response of losartan (Los) in HEK293 cells overexpressing AT1R reveals an absence of β-arrestin recruitment and G-protein activation. C and D: administration of TRV120023 to HEK293 cells expressing high (600 fM/mg) and very high (2 pM/mg) levels of AT1R did not result in accumulation of diacylglycerol (DAG) as revealed by the fluorescence resonance energy transfer-based DAG reporter (DAGR) (31).