Figure 5.

Simulation of inverse agonist/[³H]agonist competition using the extended ternary complex model (Figure 1). The extended ternary complex model for two ligands was used with the following parameters: R_tot=1 × 10⁻⁷ M, G_tot=5 × 10⁻⁸ M, L=100, J=1 × 10⁻¹⁰ M; dissociation constants for inverse agonist: K_R=1 × 10⁻¹⁰ M, K_R^*=K_R^*G; dissociation constants for agonist: K_R=5 × 10⁻⁹ M, K_R^*=1 × 10⁻¹¹ M, K_R^*G=1 × 10⁻¹¹ M. K_R^*G was varied to give the K_R/K_R^*G ratios shown, data were simulated in Excel ([agonist]=1 nM, varying concentrations of inverse agonist) and fitted using Prism as described in Methods section. Parameters derived from this analysis are given in Table 4.