Fig. 3.

Analysis of simulated agonist concentration-response curves. Agonist concentration-response curves were generated by first calculating the stimulus (a and b) using eq. 30 under Appendix with the concentration of guanine nucleotide high (X = 1.0 mM). This stimulus was used as input to the operational model (eq. 1) to yield the response as a function of the agonist concentration (c). d, nonlinear regression analysis of the concentration-response curve of agonist A using eq. 4. The points show the estimates of log RI_i, log ε, and the RSS plotted against the value to which K_E-obs was constrained during regression analysis. A least-squares fit was obtained whenever log K_E-obs ≤ −1.55. The affinity constants of the agonists (A–E) for the inactive state of the receptor were the same (K_a = 10⁵ M⁻¹). Those for the active state (K_b) were 10¹⁰, 10⁹, 10⁸, 10⁷, and 10⁶, respectively, as indicated by the K_b/K_a ratios in a and b. The microscopic state constants for the quaternary complex model were log K_e, −2.15; log K_g, 2.85; log K_k, 8.00; log K_m, 4.60; and log K_c, −4.30. The ratio of G protein to receptor was 10, and the receptor concentration was 1.0 unit. The parameters of the operational model were M_sys, 100; m, 1.0; and log K_E, −1.7.