Figure 7.
Concentration response profiles of the mOR-EG ligands supporting the ligand-induced selective signaling of the OR. Data of the mOR-EG/Gα15 and mOR-EG/Gαs(olf) assay is shown in red and blue, respectively. Ligands are grouped according to their ability to differentially signal through the mOR-EG/Gα15 and mOR-EG/Gαs(olf) pathways. (A) Ligands in this group activate both pathways with a similar affinity albeit their different efficacy. (B) Three ligands in this group show substantial selectivity towards activation of the mOR-EG/Gα15 pathway, and (C) mousse cristal is a unique ligand strongly activating both pathways yet with a different apparent affinity. Ligand concentration dependences were generated after normalization of the data to the maximal response evoked by 1mM Eugenol. Each data point is a mean ΔF/Fo ± SEM measured in 28-554 cells in 2-9 independent experiments. Solid lines show the best fit to the Hill equation (with 1.0 set as the maximum function constraint in a few cases e.g. vanillin, where response saturation could not be reached due to the solubility limit). (D) Pair-wise comparison plot of the EC50 values calculated for each ligand in mOR-EG/Gα15 (PLC based) and mOR-EG/Gαs(olf) cells (AC based). Proximity of ligands close to diagonal suggests their little if any functional selectivity. A number of ligands however appear to preferentially activate the Gα15-dependent pathway resulting in a shift off the diagonal (grey symbols).
