Table 1.
Affinity and cooperativity estimates for allosteric modulation of orthosteric agonist-mediated iCa2+ mobilization and IP1 accumulation in HEK293A-mGlu5-low and cortical neurons. Data are mean ± SEM of 3–9 independent experiments performed in duplicate.
| HEK293A: glu-iCa2+ | HEK293A: DHPG-iCa2+ | Cortical: DHPG-iCa2+ | Cortical: DHPG-IP1 | |||||
|---|---|---|---|---|---|---|---|---|
| pKBa | logβb | pKB | logβ | pKB | logβ | pKB | logβ | |
| VU0424465 | 6.94±0.19 | 0.37±0.11 | 7.00±0.11 | 0.84±0.13c | n/a | n/a | n/a | n/a |
| VU0403602 | 7.62±0.17 | 0.97±0.15 | 7.23±0.34 | 1.06±0.12 | n/a | n/a | n/a | n/a |
| VU0360172 | 6.67±0.18 | 0.53±0.13 | 7.24±0.36 | 0.52±0.07 | 7.11±0.29 | 0.75±0.10 | 6.55±0.15 | 0.20±0.09d |
| VU29 | 6.87±0.22 | 0.13±0.09 | 6.67±0.28 | 0.81±0.08c | 5.70±0.45 | 1.07±0.24 | 6.51±0.19 | 0.29±0.04 |
| CDPPB | 6.58±0.25 | 0.69±0.16 | 6.87±0.17 | 0.72±0.08 | 6.61±0.25 | 0.66±0.15 | 6.81±0.41 | 0.25±0.12 |
| DPFE | 6.04±0.27 | 0.60±0.13 | 5.35±0.25 | 1.07±0.11c | 5.45±0.22 | 0.84±0.05 | 5.50±0.23 | 0.26±0.14d |
| VU0405398 | 7.00±0.12 | 0.31±0.06 | 6.97±0.24 | 0.57±0.06c | 5.37±0.29 | 0.56±0.08 | 6.46±0.13d | 0.11±0.03d |
| VU0409551 | 5.96±0.43 | 1.00±0.27 | 5.88±0.20 | 1.06±0.09 | 6.04±0.24 | 1.16±0.27 | 6.14±0.16 | 0.35±0.13d |
pKB, negative logarithm of the equilibrium dissociation constant determined using an operational model of allosterism.
logβ, logarithm of the efficacy modulation factor.
n/a denotes operational parameters not determined due to confounding agonism.
denotes p<0.05, comparing logβ values between glutamate and DHPG-stimulated iCa2+ mobilization.
denotes p<0.05, comparing respective operational parameters between iCa2+ mobilization and IP1 accumulation for cortical neurons, using an unpaired Student’s t-test.