TABLE 3.
Effect of Org 27569 and PSNCBAM-1 on CP55940 and WIN55212-2 in the PathHunter β-arrestin assay
Increase in luminescence (relative light units, RLU) are presented as a percentage of the maximal CP55940 stimulation.
| Agonist | Vehicle/Modulator | pEC50 a | Emaxb (%) (95% CI) | % Inhibition ±SEM |
|---|---|---|---|---|
| CP55940 | DMSO | 7.9 ± 0.06 | 99.5 (95–104) | |
| Org 27569 (1 nM) | 8.1 ± 0.1 | 66.7 (60–73)† | 32.9 ± 5.2 | |
| Org 27569 (10 nM) | 8.0 ± 0.1 | 15.3 (13.5–17)† | 84.3 ± 1.1 | |
| Org 27569 (100 nM) | — | —† | 98.9 ± 0.2 | |
| WIN55212 | DMSO | 6.9 ± 0.1 | 83.5 (70–97) | |
| Org 27569 (1 nM) | 7.1 ± 0.07 | 76.4 (70–83) | 8.5 ± 2.7 | |
| Org 27569 (10 nM) | 7.0 ± 0.1 | 37.9 (33–43)† | 54.2 ± 0.7 | |
| Org 27569 (100 nM) | 7.3 ± 0.7 | 3.4 (0.3–7)† | 94.6 ± 1.7 | |
| Anandamide | DMSO | 7.4 ± 0.2 | 100.0 (83– 117) | |
| Org 27569 (1 nM) | 7.0 ± 0.1 | 110.9 (96–126) | −10.92 ± 0.6 | |
| Org 27569 (10 nM) | 6.0 ± 0.6 | —† | 80.2 ± 3.3 | |
| Org 27569 (100 nM) | 8.8 ± 1.6 | —† | 135 ± 1.8 | |
| CP55940 | DMSO | 7.9 ± 0.06 | 102.3 (98–107) | |
| PSNCBAM (1 nM) | 7.9 ± 0.1 | 76.8 (70–83)† | 24.5 ± 4.3 | |
| PSNCBAM (10 nM) | 8.6 ± 0.3 | 18.3 (15–21)† | 82.1 ± 1.2 | |
| PSNCBAM (100 nM) | — | —† | 96.9 ± 2.1 | |
| WIN55212 | DMSO | 7.6 ± 0.1 | 101.3 (90–112) | |
| PSNCBAM (1 nM) | 7.5 ± 0.1 | 90.2 (82–98) | 10.0 ± 6.6 | |
| PSNCBAM (10 nM) | 7.8 ± 0.2 | 46.1 (39–53)† | 53.8 ± 3.7 | |
| PSNCBAM (100 nM) | 8.6 ± 1.5 | 8.9 (5–13)† | 90.5 ± 2.6 |
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.