Figure 5.

Isoeugenol and mousse cristal as an examples of biased mOR-EG ligands. (A) Isoeugenol represents a group of compounds that evoke substantially reduced Gαs(olf)-dependent responses as compared to Gα15-dependent responses. (B) Mousse cristal appears to be a full agonist for mOR-EG, activating both Gα15- and Gαs(olf)-dependent response even stronger than eugenol yet with a different apparent affinity. The response to mousse cristal is also characterized by a different kinetics. Apparently, the Gα15-dependent response to mousse cristal was considerably slower than that to eugenol. Left panels (A,B) show averaged Ca²⁺ signals recorded in a single experiment. Each data point is the mean ΔF/F ± SD (grey bars) of fluorescence intensity of individual mOR-EG/Gα15 cells (red) and mOR-EG/Gαs(olf) cells (blue). Middle panels (A,B) show concentration dependence of parameters of the response kinetics for the respective ligand. Light grey symbols and scales correspond to Tpeak, dark grey symbols and scales – Trise, and black – Tdecay (see Fig.2 for parameters definition). Values are mean ± SEM. Right panels (A, B) show concentration dependence of the response amplitude for the respective ligand. Dose response of individual cells is shown in grey. Color symbols represent averaged values. All values were normalized to the response maximum activated by 1mM eugenol in individual cells. Solid smooth lines are the best fit to the Hill equation (see Table 1 for the respective parameters).