Compound | Subunit | EC50 | nHill | Max. % | n | EC50 Ratio Flop/Flip |
---|---|---|---|---|---|---|
μM | ||||||
D1 | GluR1 flop | 3.1 ± 0.5 | 2.5 ± 0.8 | 150 ± 5 | 3 | |
GluR2 flop | 4.3 ± 0.3 | 2.0 ± 0.7 | 168 ± 12 | 2 | ||
GluR2 flip | 2.7 ± 0.0* | 1.6 ± 0.2 | 217 ± 7 | 2 | 1.6 | |
GluR3 flop | 7.7 ± 0.2 | 1.5 ± 0.1 | 273 ± 38 | 3 | ||
GluR3 flip | 3.2 ± 0.6** | 1.6 ± 0.2 | 288 ± 14 | 3 | 2.4 | |
GluR4 flop | 5.0 ± 1.3 | 1.4 ± 0.1 | 198 ± 16 | 4 | ||
GluR4 flip | 0.8 ± 0.1* | 1.9 ± 0.1 | 265 ± 15 | 4 | 6.3 | |
20d | GluR4 flop | 104 ± 4 | 56 ± 10 | 2 | ||
GluR4 flip | 20 ± 3** | 132 ± 9 | 2 | 5.2 | ||
IDRA-21 | GluR4 flop | >500 | N.D. | <90 | 3 | |
GluR4 flip | 117 | 1.8 | 129 | 3 | >4 |
The selectivity for AMPA receptor subunits was determined as described in Fig. 9 by measuring the effect of the drug on the binding of (S)-[3H]AMPA. Binding incubations were conducted at 0°C with a fixed concentration of (S)-[3H]AMPA in the absence of KSCN. They were terminated by filtration through GF/C glass fiber filters. (S)-AMPA concentrations were selected between 10 and 50 nM to obtain approximately 10 to 20% receptor occupancy in the absence of drug. In each experiment, binding was measured at seven to nine drug concentrations and fitted with a four-point logistic equation. Binding constants from the indicated number of experiments were then averaged (means and S.E.M.). To obtain the binding parameters for the effect of IDRA-21, binding data from three experiments were first averaged and then fitted; its effect on GluR4 flop was fitted with ann Hill = 1 because of the smallness of the binding change.
N.D., not determined.
Differences in EC50 values between flip and flop were significant as indicated; *, P < 0.05, **,P < 0.01.