Potencies and efficacies for dopamine and (−)-quinpirole at wild-type and mutant D4 receptors
Data for the potencies (EC50, nM) and relative efficacies of dopamine and (−)-quinpirole are expressed as the mean ± S.D. of three separate experiments. Relative efficacy is defined as the percentage decrease in cAMP levels relative to the level of cAMP generated by 6 μM forskolin minus basal levels of cAMP. Increased (↑) or decreased (↓) values relative to the wild-type D4 receptor are expressed as fold changes within parentheses. Significance relative to the wild-type D4 receptor was determined by one-way ANOVA with Dunnett's post hoc (*, P < 0.05). N.D., not determined.
| Receptor | Dopamine | (−)-Quinpirole | ||
|---|---|---|---|---|
| EC50 | Relative Efficacy | EC50 | Relative Efficacy | |
| nM | % | nM | % | |
| Wild-type D4 | 85 ± 72 (1) | 72 ± 18 (1) | 17 ± 7.7 (1) | 48 ± 13 (1) |
| D4-S5.42A | >10,000a (>118↑) | N.D.a (4.5↓) | 25 ± 19 (1.5↑) | 57 ± 6.6 (1.2↑) |
| D4-S5.43A | 3487 ± 561* (41↑) | 75 ± 28 (1) | 22 ± 11 (1.3↑) | 45 ± 6.9 (1.1↓) |
| D4-S5.46A | N.D. | N.D. | 86 ± 55 (5↑) | 46 ± 9.1 (1) |
↵a Dopamine potency in the S5.42A mutant is estimated at more than 10 μM and the maximal effect cannot be determined.