Functional response, as measured by the phosphoinositide turnover assays, caused by ligand binding to wild-type and Tyr381 mutant M1 mAChRs
| Wild-Type | Tyr381Phe | Tyr381Ala | ||||
|---|---|---|---|---|---|---|
| pEC50 | % Response4-a | pEC50 | % Response4-a | pEC50 | % Response4-a | |
| ACh | 6.99 ± 0.08 | (100) | 5.17 ± 0.04 | 125 ± 5 | 3.55 ± 0.13 | 118 ± 10 |
| ACh-reversed ester | 5.32 ± 0.05 | 83 ± 3 | 3.99 ± 0.04 | 86 ± 9 | 3.03 ± 0.02 | 35 ± 1 |
| Tetramethylammonium | 3.87 ± 0.06 | 85 ± 5 | 3.05 ± 0.02 | 49 ± 6 | No Measurable Response | |
| L-698,583 | 9.09 ± 0.14 | 102 ± 2 | 7.12 ± 0.03 | 126 ± 1 | 5.08 ± 0.06 | 118 ± 1 |
| L-658,903 | 7.75 ± 0.10 | 89 ± 7 | 6.34 ± 0.05 | 91 ± 15 | 4.32 ± 0.30 | 46 ± 5 |
Values are mean ± S.E. from three experiments except for the functional response caused by ACh binding to wild-type M1mAChR, which was determined from nine experiments. The Hill coefficients ranged from 0.8 to 1.2 with the possible exception of ACh-reversed ester at the wild-type receptor.
↵4-a The response has been measured as a percentage of the fold basal response produced by ACh at the wild-type M1 mAChR. The maximum response produced by ACh binding as measured by fold basal (and basal response) at wild-type, Tyr381Phe, and Tyr381Ala were 4.4 ± 0.4 (475 ± 32 dpm), 5.5 ± 0.3 (379 ± 30 dpm), and 5.2 ± 0.6 (332 ± 32 dpm), respectively.