Figure 4.

Key interactions between 5-HT_2C and 1857 specifically modulate the agonist activity. Docking poses of 1857 (A) and lorcaserin (B) in 5-HT_2C. Predicted key interacting residues are in purple. (B) V354^7.39 in gray does not interact with lorcaserin. Radiolabeled ligand binding curves (upper) and G_q-mediated calcium flux (lower) in cells expressing wild-type (WT) or mutant 5-HT_2C in the presence of 1857 (C) or lorcaserin (D). (E) β-arrestin2 recruitment in cells expressing WT or mutant 5-HT_2C in the presence of 1857 (upper) or lorcaserin (lower). G_q activity of 5-HT_2C elicited by 1857 was significantly affected by mutations on five key interaction sites relative to WT, yet they hardly changed G_q activity of 5-HT_2C treated by lorcaserin. See also Table S5 for IC₅₀/EC₅₀ values. Data represent means ± SEM of three independent experiments performed in triplicate.