Table 1.
Maximal effects and EC50 values of the tested compounds on mGlu8 receptors and its mutants
| Compound | mGlu8-wt | mGlu8-D309E | mGlu8-D309A | mGlu8-Y227F | mGlu8-Y227A |
|---|---|---|---|---|---|
| Maximal, %AP4 | |||||
| Glu | 96 ± 3 (7) | 100 ± 4 (7) | 68 ± 9 (8) | 90 ± 3 (7) | 81 ± 2 (8) |
| L-AP4 | 100 | 100 | 100 | 100 | 100 |
| ACPT-II | Ant (6) | Ant (4) | 99 ± 18 (8) | n.t. | n.e. (1) |
| MAP4 | Ant (5) | n.e. (1) | n.e. (1) | 26 ± 4 (8) | 85 ± 4 (6) |
| EC50, μM | |||||
| Glu | 15 ± 4 (5) | 66 ± 9 (4) | 790 ± 190 (3) | 28 ± 3 (2) | 103 ± 6 (2) |
| L-AP4 | 0.2 ± 0.1 (3) | 4.1 ± 0.8 (4) | 124 ± 14 (2) | 3.7 ± 1.2 (2) | 5.2 ± 1.2 (2) |
| ACPT-II | (Ki 50) | ND | 40 ± 6 (2) | — | — |
| MAP4 | (Ki 53) | — | — | 25 ± 13 (2) | 11 ± 1 (2) |
The maximal IP production measured with 1 mM l-glutamate, L-AP4, ACPT-II, or MAP4 in cells expressing the indicated receptor is expressed as the percentage of that measured with 1 mM L-AP4 and is mean ± SEM of (n) independent experiments performed in triplicate. The 1 mM L-AP4 effect measured on mGlu8-D309E, -D309A, Y227F, and Y227A is equal to 109 ± 15, 30 ± 3, 180 ± 22, and 153 ± 10% of that measured on control cells (n = 7, 11, 5, and 4, respectively). The EC50 values shown were determined as described in the text and are means ± SEM of n independent determinations. n.t., not tested; n.e., no agonist effect; Ant, antagonist property; ND, not determined. Ki values were calculated based on published data (34).