Table 3. Summary of Qualitative and Quantitative Cooperativity Estimates (log β) for mGlu5 NAMs at Mutant Constructsa.
| mutant | M-5MPEP | VU0366058 | VU0285683 | VU0409106 | VU0366248 | VU0366249 |
|---|---|---|---|---|---|---|
| R5-wt | –1.00 ± 0.11 | Full NAM | Full NAM | Full NAM | –0.88 ± 0.11 | –0.66 ± 0.18 |
| P654F | Weak NAM | No NAM | No NAM | No NAM | No NAM | No NAM |
| P654S | –0.37 ± 0.08b | –0.45 ± 0.08 | Full NAM | Full NAM | –0.30 ± 0.09b | Weak NAM |
| S657C | Full NAM | n.d. | n.d. | n.d. | Full NAM | –0.23 ± 0.07 |
| S657A | Full NAM | n.d. | n.d. | n.d. | Full NAM | Full NAM |
| Y658V | Weak NAM | -0.36c | Full NAM | –0.75 ± 0.10 | Full NAM | No NAM |
| P742S | Full NAM | n.d. | Full NAM | n.d. | n.d. | No NAM |
| N746A | Full NAM | –0.39 ± 0.15 | Full NAM | Full NAM | –1.20 ± 0.08 | Weak NAM |
| G747V | –0.46 ± 0.18 | Full NAM | Full NAM | Full NAM | Full NAM | Full NAM |
| T780A | –0.56 ± 0.08 | –0.55 ± 0.06 | Full NAM | –0.82 ± 0.09 | Full NAM | Weak NAM |
| W784A | No NAM | –0.50 ± 0.17 | 0.27 ± 0.06 | –0.43 ± 0.08 | 0.29 ± 0.05b | 0.36 ± 0.06b |
| F787A | Full NAM | Full NAM | Full NAM | Full NAM | No NAM | No NAM |
| V788A | –0.72 ± 0.22 | Full NAM | Full NAM | Full NAM | Full NAM | Full NAM |
| F792A | n.d. | n.d. | n.d. | Full NAM | Full NAM | n.d. |
| S808A | –0.66 ± 0.11 | –0.44 ± 0.10 | –0.59 ± 0.14 | Full NAM | –0.80 ± 0.35 | No NAM |
| S808T | –0.55 ± 0.19 | –0.39 ± 0.09 | –0.77 ± 0.19 | Full NAM | Full NAM | Full NAM |
| A809V | Full NAM | Full NAM | Full NAM | Full NAM | Full NAM | No NAM |
| A809G | –0.43c | –0.52 ± 0.10 | Full NAM | Full NAM | –0.48 ± 0.07 | No NAM |
a
Data are mean ± SEM of 3–5 independent experiments, unless noted otherwise. “Weak NAM” denotes incomplete and nonsaturating inhibition of the glutamate response. “Full NAM” denotes complete abolishment of the glutamate Ca2+ mobilization response. “No NAM” indicates no inhibition of the glutamate response was observed up to 10 μM. n.d. denotes not determined. Mutations of the six common determinant residues are highlighted in bold text.
b
Significantly different to wild type, one-way ANOVA, p < 0.05 Dunnett’s post-test.
c
Data are mean from two independent experiments.