Table 4.

Simulated competition of a [³H]agonist by an inverse agonist

KR/KR*G	5	10	20	40	80	160	320
Kuncoupled (nM)	0.11	0.11	0.11	0.12	0.12	0.12	0.12
Kcoupled (nM)	0.28	0.41	0.54	0.65	0.73	0.77	0.80
Kuncoupled/Kcoupled	2.55	3.73	4.91	5.41	6.08	6.42	6.67
%Rh	36.3	36.8	37.2	37.6	37.8	37.9	38.0

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. Simulated data were fitted best by two-binding site models in all cases and values for K_uncoupled, K_coupled and %R_h were derived as described in the text.