Allosteric model parameter estimates for the interaction between LY2033298 and [3H]QNB at M2 mAChRs
Values represent the mean ± S.E.M. from at least three experiments performed in duplicate.
| [3H]QNB | |||||
|---|---|---|---|---|---|
| WT | W99A3.28 | Y104A3.33 | Y177A | Y403A6.51 | |
| pKBa | 4.74 ± 0.06 | 4.20 ± 0.07* | 3.79 ± 0.17* | N.D. | 4.44 ± 0.10 |
| logα′b | −3d | −3d | 1.18 ± 0.12 | N.D. | 0.64 ± 0.04 |
| α′c | 0.001 | 0.001 | 15 | N.D. | 4.4 |
N.D., not determined.
↵* Significantly different from the corresponding value at the wild type (P < 0.05).
↵a Negative logarithm of the allosteric modulator equilibrium dissociation constant.
↵b Logarithm of the cooperativity factor for the interaction between LY2033298 and the orthosteric radioligand.
↵c Antilogarithm of the cooperativity factor.
↵d Values were not significantly different from −3 and were therefore constrained to such value. This is indicative of a negative allosteric interaction that is indistinguishable from competition (α′ → 0).