Figure 4.

(A) Semilog concentration–response curves with the present model for a receptor without constitutive activity (Equation 4, Figure 1C ) and ligands with 100 nM affinity (K _d = 10^–7 M). Response curves shown are for a full and a weak partial agonist (ε=1, blue lines and ε=0.25, red lines, respectively) at different amplifications (γ=1, 3, and 100; denoted with full and dashed lines, respectively). Another partial agonist without amplification is also included (ε=0.70, γ=1 orange line) for comparison. Note that with the present model, the basic parametrization (ε=1, γ=1) fully reproduces the Clark model (blue and double green lines completely overlap), which could not be done with previous models such as the operational model. (B) Illustrative response curves with the present model for a case with constitutive activity (ε _R0=0.3) and no amplification ( Figure 1B ). Response curves for full, partial, and inverse agonists as well as a neutral antagonist with the same affinity as in A (K _d = 10^–7 M) are shown as obtained with the efficacy parametrization of the present model.