Affinity of a panel of compounds at wild-type, active-state, and inactive-state StaRs as measured by competition radioligand binding
An unpaired, two-tailed t test was used to compare affinity of compounds at A2A and A2A(1-316); there was no significant difference at any compound tested (P > 0.05). By comparing affinity of compounds at StaR2(1-316) and A2A(1-316) with an unpaired two-tailed t test, it was revealed that NECA had a significantly reduced affinity at StaR2(1-316). All data were generated using [3H]NECA as the radioligand, except for StaR2(1-316) where [3H]ZM241385 was used due to the low affinity of agonists for this construct. pKi displayed as mean ± S.E.M. of n = 3–5.
| Wild Type | Active State | Inactive State | |||||
|---|---|---|---|---|---|---|---|
| A2A | A2A(1-316) | GL0 | GL23 | GL26 | GL31 | StaR2(1-316) | |
| NECA | 8.14 ± 0.20 | 7.82 ± 0.20 | 8.67 ± 0.10** | 8.60 ± 0.05 | 8.51 ± 0.13 | 8.86 ± 0.04** | 6.07 ± 0.20†† |
| Caffeine | 5.44 ± 0.15 | 5.78 ± 0.18 | 4.97 ± 0.54 | 5.02 ± 0.42 | 4.40 ± 0.25 | 4.83 ± 0.40 | 5.19 ± 0.16† |
| Istradefylline | 7.42 ± 0.14 | 7.12 ± 0.14 | 7.38 ± 0.26 | 7.54 ± 0.10 | 7.50 ± 0.24 | 7.86 ± 0.08 | 7.38 ± 0.24 |
| Theophylline | 5.74 ± 0.09 | 5.94 ± 0.14 | 5.15 ± 0.49 | 5.05 ± 0.39 | 4.37 ± 0.19 | 4.91 ± 0.34 | 5.36 ± 0.15† |
| ZM241385 | 9.17 ± 0.23 | 9.22 ± 0.04 | 7.30 ± 0.03*** | 7.18 ± 0.24*** | 6.77 ± 0.15*** | 7.68 ± 0.02*** | 8.60 ± 0.19 |
| XAC | 8.41 ± 0.47 | 8.56 ± 0.04 | 6.93 ± 0.05*** | 6.72 ± 0.01*** | 7.06 ± 0.04*** | 7.86 ± 0.02* | 8.38 ± 0.21 |
| SCH58261 | 8.89 ± 0.19 | 8.86 ± 0.13 | 6.30 ± 0.09*** | 6.05 ± 0.23*** | 4.51 ± 0.21*** | 4.56 ± 0.08*** | 8.42 ± 0.12 |
| Preladenant | 8.95 ± 0.06 | 8.76 ± 0.12 | 6.33 ± 0.05*** | 4.63 ± 0.10*** | 4.63 ± 0.10*** | 6.29 ± 0.04*** | 8.63 ± 0.05 |
* P < 0.05; ***P < 0.001, when comparing affinity at active state receptors to A2A (one-way ANOVA with Dunnett’s post-hoc test).
† P < 0.05; ††P < 0.01.