Table 1.

Potency, maximal response and operational model parameters for agonist-mediated ERK1/2 phosphorylation

	Human M4 mAChR		Mouse M4 mAChR
Parameter	ACh	LY2033298	ACh	LY2033298
pEC50a	7.89 ± 0.09	7.03 ± 0.09	7.09 ± 0.09*	6.13 ± 0.12*
Emaxb	80.9 ± 2.3	78.5 ± 2.9	55.9 ± 1.8*	48.8 ± 2.9*
pKBc	n.a.	5.39 ± 0.05	n.a.	5.49 ± 0.31
Logτd	n.a.	1.59 ± 0.05	n.a.	0.66 ± 0.22*

Data represent mean ± SEM of four to five experiments performed in duplicate.

^*Significantly different (P < 0.05) from the corresponding value at the human receptor, as determined by Student's t-test.

^aNegative logarithm of the midpoint potency parameter.

^bMaximum agonist effect, expressed as a percentage of the ERK1/2 phosphorylation response elicited by 10% FBS.

^cNegative logarithm of the LY2033298 equilibrium dissociation constant, obtained from a global fit of an operational of agonism to the ACh and LY2033298 data sets.

^dLogarithm of the operational efficacy estimate.

n.a., not applicable.