TABLE 4

Allosteric operational model binding parameters for various modulators at mouse vas deferens CB1 receptors All data sets (shown in Fig. 6) were globally analyzed using eq. 5 under Materials and Methods. The best-fit parameter values describing the activity of WIN 55,212 across the data sets were as follows: pKA = 6.86 ± 0.28; Log τ = 1.97 ± 0.33; Em = 82.7 ± 3.6; and n = 0.86 ± 0.18. pKB is the negative logarithm of the equilibrium dissociation constant for the allosteric modulator at the free receptor, determined using nonlinear regression according to eq. 2 under Materials and Methods. Values represent the mean ± S.E. of four to eight experiments. Log α is the logarithm of the cooperativity factor. α is the antilogarithm (geometric mean) of the cooperativity factor, based on the estimated log α values. β is the empirical coupling constant, quantifying the fractional stimulus imparted by the modulator-occupied ternary complex.

Parameter Allosteric Modulator
Org 27569 Org 27759 Org 29647
pKB 7.57 ± 0.15 6.87 ± 0.28 7.46 ± 0.32
Log α 1.20 ± 0.15 1.32 ± 0.27 1.35 ± 0.19
α 16 (11.2—22.4) 21 (11.2—38.9) 22 (14.4—34.7)
β 0.006 ± 0.002 0 ± 0.002 0.018 ± 0.007