TABLE 2.
Effect of Org 27569 on CP55940 and WIN55212 in [35S]GTPγS binding, cAMP, and pERK assay in hCB1R cells
| Agonist | Vehicle/Modulator | pEC50 a | Emax b (%) (95% CI) | % Inhibition SEM |
|---|---|---|---|---|
| [35S]GTPγS Binding (% Stimulation above Basal) | ||||
| CP55940 | DMSO | 7.3 ± 0.2 | 64.7 (57–72) | |
| Org 27569 (10 nM) | 6.2 ± 0.4 | 76.2 (48–105) | 13.8 ± 31 | |
| Org 27569 (100 nM) | 6.9 ± 0.6 | 35.2 (19–52)† | 46.3 ± 18 | |
| Org 27569 (1 μM) | — | —† | 94.4 ± 6.0 | |
| WIN55212 | DMSO | 6.7 ± 0.2 | 70.4 (62–79) | |
| Org 27569 (100 nM) | 6.5 ± 0.3 | 67.7 (49–87) | 1.2 ± 16 | |
| Org 27569 (1 μM) | 6.9 ± 0.4 | 33.1 (20–47)† | 43.4 ± 18 | |
| cAMP Assay (% Inhibition of Forskolin Stimulation) | ||||
| CP55940 | DMSO | 8.1 ± 0.2 | 86.6 (75–98) | |
| Org 27569 (10 nM) | 7.6 ± 0.4 | 55.0 (37–73)† | 30.3 ± 12.0 | |
| Org 27569 (100 nM) | — | —† | 155 ± 9.6 | |
| WIN55212 | DMSO | 7.1 ± 0.2 | 78.6 (64–93) | |
| Org 27569 (100 nM) | 7.0 ± 0.2 | 64.6 (51–78) | 22.3 ± 4.9 | |
| Org 27569 (1 μM) | 6.9 ± 0.3 | 41.1 (23–59)† | 37.0 ± 5.9 | |
| ERK1/2 Phosphorylation (% Increase above Basal) | ||||
| CP55940 | DMSO | 7.6 ± 0.14 | 50.0 (44–56) | |
| Org 27569 (100 nM) | 8.0 ± 0.16 | 72.0 (64–80)† | — | |
| Org 27569 (1 μM) | 7.8 ± 0.23 | 65.0 (58 -72)† | — | |
| WIN55212 | DMSO | 6.6 ± 0.53 | 40.2 (27–54) | |
| Org 27569 (100 nM) | 7.0 ± 0.67 | 50.9 (35–66) | — | |
| Org 27569 (1 μM) | 6.6 ± 0.48 | 37.0 (24–51) | — | |
a
Negative logarithm of the agonist EC50 value, determined using nonlinear regression analysis. Values represent the mean ± standard error of the mean (S.E.M.) of four to six experiments.
b
Maximal agonist effect, determined using nonlinear regression analysis. Values represent the mean with 95% CI of four to six experiments.
†
Significantly different (nonoverlapping confidence limits) from the DMSO vehicle.