TABLE 4.
Summary of operational model parameters for allosteric modulation of glutamate-mediated ERK1/2 phosphorylation in HEK cells expressing low mGlu5 levels
For ERK1/2 phosphorylation in the low-level mGlu5-expressing cell line, data were expressed as fold increases over basal values, with the Em defined as the response to 10% fetal bovine serum (9.4-fold). In the presence of allosteric modulators, logτA (−0.36 ± 0.13) and n (4.43 ± 0.50) were not significantly different (one-way analysis of variance) (Supplemental Table 3). Parameters are as defined for Table 2. Data represent the mean ± S.E.M. from at least three independent determinations.
| Modulator | pKB | logβ | logτB |
|---|---|---|---|
| Positive allosteric modulators | |||
| CDPPB | 7.39 ± 0.18 | 0.13 ± 0.05 | −0.05 ± 0.11 |
| VU29 | 7.63 ± 0.25* | 0.25 ± 0.10 | −0.07 ± 0.08 |
| CPPHA | 6.88 ± 0.14 | 0.05 ± 0.02 | −0.13 ± 0.05 |
| VU0357121 | 7.56 ± 0.30 | 0.03 ± 0.02 | −0.17 ± 0.08 |
| VU0364289 | 6.29 ± 0.11* | 0.16 ± 0.02 | 0.04 ± 0.05 |
| VU0092273 | 7.16 ± 0.08 | 0.11 ± 0.02 | 0.01 ± 0.02 |
| VU0360172 | 7.16 ± 0.26 | 0.12 ± 0.04 | 0.00 ± 0.03 |
| VU0405398 | 7.62 ± 0.32 | 0.05 ± 0.05 | −0.39 ± 0.20 |
| VU0415051 | 8.32 ± 0.21 | 0.03 ± 0.02 | −0.27 ± 0.08 |
| VU0405386 | 8.45 ± 0.19 | 0.19 ± 0.07 | 0.00 ± 0.11 |
| Negative allosteric modulators | |||
| MPEP | 8.20 ± 0.32 | −100 | |
| M-5MPEP | 6.60 ± 0.07 | −100 | |
| VU0285683 | 7.74 ± 0.14 | −100 | |
| VU0366248 | 6.37 ± 0.23 | −100 | |
| VU0366249 | 6.40 ± 0.19 | −0.31 ± 0.12 | |
| VU0366058 | 7.23 ± 0.25 | −100 |
Significantly different (P < 0.05) from the value for the modulator determined in low-level mGlu5-expressing HEK293A cells for Ca2+ mobilization, with one-way analysis of variance and Tukey's post hoc test.