Table 4

Multicomponent analysis of agonist displacement of [3H]SR141716A and stimulation of [35S]GTPγS binding in hippocampal membranes

Agonist Site[3H]SR141716A Binding[35S]GTPγS BindingKi/Ks Ratio
nH%Log IC50(Ki)nH%Log EC50 (Ks)
nM nM
WIN55212-20.530.73
 High22−8.50  ± 0.51 (1.01)
 Intermediate59−6.81  ± 0.29 (50.8)32−7.46  ± 0.26 (11.4)4.5
 Low19−5.01  ± 0.62 (3200)68−6.20  ± 0.14 (207)15.5
Levonantradol0.500.66
 High29−9.31  ± 0.24 (0.16)
 Intermediate29−7.75  ± 0.62 (5.73)60−7.89  ± 0.12 (4.20)1.4
 Low42−6.57  ± 0.23 (87.3)40−6.49  ± 0.24 (105)0.83
CP559400.560.56
 High29−9.11  ± 0.54 (0.25)
 Intermediate14−8.04  ± 2.52 (2.94)55−8.13  ± 0.13 (2.43)1.3
 Low57−6.87  ± 0.22 (44.0)45−6.38  ± 0.23 (137)0.32
Methanandamide0.860.67
 High24−6.87  ± 0.52 (44.3)14−7.46  ± 0.45 (11.2)4.0
 Low76−5.80  ± 0.18 (517)86−5.61  ± 0.09 (789)0.66

Agonist concentration-effect curves were generated under identical assay conditions for displacement of [3H]SR141716A binding and stimulation of [35S]GTPγS binding. Data were normalized to percentage of total specific (or agonist-stimulated) binding. Pooled data from seven separate experiments were fit to multicomponent equations by nonlinear regression, as described underExperimental Procedures. The “%” column refers to the percentage of total binding sites that are of high, intermediate, or low affinity as fit by nonlinear regression. IC50 and EC50 values are presented as mean log values ± S.E. of each fit, with corresponding Ki andKs values in nM listed in parentheses.Ki/Ks ratios are shown for receptor binding and [35S]GTPγS-stimulating sites that are hypothesized to correspond to one another.