Table 2.
Allosteric model co-operativity parameters (Logαβ) for the functional interaction between LY2033298 and orthosteric agonists at the M4 mAChR
| Agonist | ERK1/2 | GSK-3α | [35S]-GTPγS |
|---|---|---|---|
| ACh (human) | 1.75 ± 0.23 (56) | 2.29 ± 0.13 (194) | 1.97 ± 0.03 (93) |
| ACh (mouse) | 1.29 ± 0.06* (19) | 0.89 ± 0.36* (8) | 1.62 ± 0.08* (42) |
| Oxotremorine (human) | n.d. | 2.24 ± 0.51 (173) | n.d. |
| Oxotremorine (mouse) | 1.89 ± 0.09 (77) | 2.29 ± 0.17 (194) | 2.51 ± 0.06 *(326) |
| Xanomeline (mouse) | 0.18 ± 0.12* (1.5) | n.d. | 0.83 ± 0.01 *(7) |
Values represent the mean ± SEM from three to five experiments performed in triplicate and derived from application of Equation 2. Antilogarithms are shown in parentheses.
*
Significantly different (P < 0.05) from the corresponding value for ACh at the human receptor, as determined by one-way anova and Dunnett's post-test.
n.d., not determined.