Fig. 7.

The VU0255035 antagonism of M₁ mAChR responses are right-shifted by Y381A mutation. A, CRCs of ACh and NDMC were performed on both wild-type (WT) and Y381A-mutated M₁ mAChRs in a calcium mobilization assay. Data were normalized to either the maximum response to 1 μM ACh (WT) or to 10 mM ACh (Y381A) and are presented as the percentage of maximal ACh response. The EC₅₀ values for ACh were 2.5 ± 0.3 nM (WT) or 13.7 ± 1.6 μM (Y381A). The EC₅₀ values for NDMC were 140.5 ± 26.1 nM (WT) or 162.4 ± 6.1 nM (Y381A). B, CRCs of VU0255035 were performed in the presence of an EC₈₀ concentration of ACh or NDMC for WT and Y381A M₁ mAChRs in a calcium mobilization assay. Data were normalized to the percentage of either the EC₈₀ ACh response or the EC₈₀ NDMC response. The IC₅₀ values for VU0255035 versus ACh were 53.3 ± 7.7 nM (WT) or 38.9 ± 0.2 μM (Y381A). The IC₅₀ values for VU0255035 versus NDMC were 57.3 ± 3.5 nM (WT) or 33.4 ± 8.4 μM (Y381A). All data points represent the mean of three independent experiments performed in triplicate, and error bars represent S.E.M.