Fig. 1: The complete signaling profile of 5-HT at the 5-HT2AR in HEK293 cells.
From: Pharmacological fingerprint of antipsychotic drugs at the serotonin 5-HT2A receptor
a The complete G protein-activation profile of 5-HT (1 µM; 15 min) in HEK293 cells heterologously expressing the untagged 5-HT2AR and the biosensor (RlucII-Gγ5/GRK2-D110A-GFP10, Gβ1 and the respective Gα subunits). Results are expressed as BRET ratio (GFP10/RlucII) as % of mock condition (in the absence of heterologously expressed Gα subunit) (mean ± SEM; n = 3; one-way ANOVA followed by Dunnett’s post hoc: **p = 0.0029, ***p = 0.0009, and ****p < 0.0001 compared to the mock condition). Concentration response curves showing the activation of the Gαq family (b), Gαi/o/z family (c), Gα12 (d), Gα13 (e), Gαs (f), as well as the recruitment of β-arrestin1 (g) or β-arrestin2 (h) using the ebBRET-based EMTA biosensor in HEK293 cells heterologously expressing the untagged 5-HT2AR, the following biosensors (rGFP-CAAX along with p63-RlucII for Gαq, Rap1GAP-RlucII for Gαi/o/z, PDZ-RlucII for Gα12 and Gα13, Gαs67-RlucII for Gαs, β-arrestin1-RlucII or β-arrestin2-RlucII for β-arrestins), the respective Gα subunits (Gαq family, Gαi/o/z family, Gα12/13), Gβ1 and Gγ1 (Gαs) or WT-GRK2 (β-arrestins). The HA-TPα receptor (U46619) was used as the positive control for Gα12/13 while the 5-HT7A receptor (5-HT) was used as the positive control for Gαs. Results are expressed as BRET ratio (rGFP/RlucII), as % over vehicle (mean ± SEM; n = 3).
