The potency and efficacy of ligands at D3/2 receptor-G protein fusions
Experiments were performed in triplicate to n = 3. %DA, Emax value of [35S]GTPγS binding compared with maximal dopamine stimulation. The potency of the ligands that were able to activate each of the four different D3/2 receptor-Gα subunit fusion proteins were compared using a one-way ANOVA with a Bonferroni post-hoc test. Significant differences in pEC50 between D3/2 receptor fusion proteins for dopamine, D3/2Gαo1 = D3/2Gαi3 > D3/2Gαi2 = D3/2Gαi1 (p < 0.001); and quinpirole, D3/2Gαo1 = D3/2Gαi3 > D3/2Gαi2 = D3/2Gαi1 (p < 0.01).
D3/2Gαi1 | D3/2Gαi2 | D3/2Gαi3 | D3/2Gαo1 | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| pEC50 (±S.E.M.) | Emax | pEC50 (±S.E.M.) | Emax | pEC50 (±S.E.M.) | Emax | pEC50 | Emax | |||||
| %DA (±S.E.M.) | %DA (±S.E.M.) | %DA (±S.E.M.) | %DA (±S.E.M.) | |||||||||
| Dopamine | 5.3 (0.06) | 100 | 5.6 (0.18) | 100 | 7.2 (0.32) | 100 | 7.3 (0.12) | 100 | ||||
| m-Tyramine | N.A. | 4.1 (0.16) | 53 (9) | 6.2 (0.17) | 81 (9) | 6.4 (0.09) | 79 (3) | |||||
| p-Tyramine | N.A. | N.A. | 5.5 (0.14) | 45 (5) | 5.2 (0.16) | 80 (1) | ||||||
| R-(+)-3-PPP | N.A. | 4.1 (0.24) | 68 (11) | 6.1 (0.08) | 68 (7) | 6.0 (0.14) | 92 (4) | |||||
| S-(-)-3-PPP | N.A. | N.A. | 6.7 (0.36) | 40 (3) | 6.9 (0.10) | 50 (4) | ||||||
| Quinpirole | 5.6 (0.09) | 120 (13) | 5.3 (0.69) | 120 (3) | 7.4 (0.21) | 100 (4) | 7.6 (0.08) | 100 (3) | ||||
| NPA | 9.4 (0.08) | 120 (12) | 8.6 (0.06) | 120 (1) | 9.3 (0.03) | 91 (3) | 9.1 (0.02) | 110 (2) | ||||
| 7-OH-DPAT | 10 (0.19) | 76 (8) | N.A. |
| 11 (0.88) | 34 (5) | 10 (0.03) | 64 (1) | ||||
N.A., no detectable stimulation.