Effect of CB receptor agonists on forskolin-stimulated cAMP accumulation in CHO cells expressing the hCB1 cannabinoid receptor
| Ligand | Receptor binding affinity | Inhibition of forskolin-stimulated cAMP accumulation | Stimulation of forskolin-stimulated cAMP accumulation | ||
|---|---|---|---|---|---|
| pKi | pEC50 | % inhibition | pEC50 | % stimulation | |
| Anandamide | 6.2 ± 0.1 | 5.7 ± 0.1 | 80 ± 3 (81%) | 5.3 ± 0.1 | 34 ± 5 (27%)1-a |
| CP-55,940 | 8.6 ± 0.2 | 8.9 ± 0.1 | 91 ± 1 (92%) | 7.8 ± 0.2 | 52 ± 1 (45%) |
| HU-210 | 9.2 ± 0.3 | 9.9 ± 0.2 | 87 ± 3 (88%) | 9.3 ± 0.2 | 66 ± 18 (57%) |
| THC | 7.5 ± 0.2 | 8.3 ± 0.1 | 47 ± 2 (47%) | 7.6 ± 0.5 | 38 ± 7 (33%) |
| WIN-55212-2 | 7.5 ± 0.4 | 7.1 ± 0.2 | 99 ± 1 (100%) | 6.2 ± 0.1 | 116 ± 10 (100%) |
Values are the mean ± S.E.M. for six concentration-response curves. Forskolin (1 μM) increased cAMP accumulation from a basal value of 0.5 to 1.5 pmol/assay well to 25 to 40 pmol/assay well. The activity values are the percent change in cAMP accumulation. Numbers in parentheses are activity values normalized to those of WIN-55212-2.
↵1-a An SR141716A-insensitive component of the anandamide-evoked response was subtracted so as to derive the CB1receptor-mediated component of the response (see fig. 4). The differences in activities for anandamide and CP-55,940 were statistically significant (P < .05), as was the interaction between transduction pathway and activity (two-way analysis of variance, P < .01). pEC50 and pKivalues are the negative log of the molar EC50 andKi values, respectively.