Table 3

Agonist potencies for inhibition of [3H]SR141716A binding, stimulation of [35S]GTPγS binding, and inhibition of adenylyl cyclase ([32P]cAMP) determined using a one-site model

Ki[3H]SR141716AKs[35S]GTPγSIC50[32P]cAMP
nM
Cerebellum
 WIN55212-211  ± 3250  ± 8342  ± 14
 Levonantradol2.3  ± 0.360  ± 17
 CP559401.7  ± 0.535  ± 7
 Methanandamide150  ± 101100  ± 260155  ± 38
 Δ9-THC110  ± 521600  ± 48032  ± 17
Hippocampus
 WIN55212-229  ± 5130  ± 39
 Levonantradol4.9  ± 1.011  ± 2
 CP559405.6  ± 1.48.5  ± 2.0
 Methanandamide330  ± 46630  ± 170
 Δ9-THC170  ± 82130  ± 48
Hypothalamus
 WIN55212-214  ± 4170  ± 64
 Levonantradol2.9  ± 1.345  ± 27
 CP559402.0  ± 1.114  ± 6
 Methanandamide240  ± 511000  ± 410
 Δ9-THC37  ± 1538  ± 12

Agonist concentration-effect curves were generated under identical assay conditions for competition for [3H]SR141716A binding and stimulation of [35S]GTPγS binding. Three representative compounds also were assayed in cerebellar membranes for inhibition of adenylyl cyclase ([32P]cAMP). Curves were fit by iterative nonlinear regression to one-site models with variable Hill slopes to obtain IC50 and EC50 values. Ki andKs values for binding were calculated as described under Experimental Procedures. Data shown are mean ± S.E. from four assays performed in duplicate.