Functional activity in phosphatidyl inositol hydrolysis assays of muscarinic agonists on rat M1 receptors containing mutations in TM3
Max Resp represents the maximum response of the receptor to each ligand normalized relative to the maximum response of the wild-type receptor to that ligand. Values represent the mean of three to six separate determinations ± S.E.M. in each case. Shift represents the EC50 for the mutant receptor divided by the EC50 for the wild-type receptor. Where the response was too low, pEC50 was not determined (denoted N.D.).
Carbachol | AC-260584 | Clozapine | N-Desmethylclozapine | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Eff | pEC50 | Shift | Eff | pEC50 | Shift | Eff | pEC50 | Shift | Eff | pEC50 | Shift | |||||||||
| % | % | % | % | |||||||||||||||||
| M1 WT | 100 ± 4 | 6.3 ± 0.2 | 1 | 100 ± 7 | 7.3 ± 0.1 | 1 | N.R. | N.D. | 55 ± 8 | 7.0 ± 0.2 | 1 | |||||||||
| W101A | >75 | <4.5 | >30 | 112 ± 6 | 8.8 ± 0.1 | 0.03 | 57 ± 11 | 8.1 ± 0.1 | 54 ± 11 | 6.5 ± 0.2 | 6 | |||||||||
| Y106A | N.R. | N.D. | 110 ± 22 | 6.6 ± 0.1 | 4 | 95 ± 21 | 8.9 ± 0.2 | 40 ± 4 | 6.7 ± 0.1 | 3 | ||||||||||
| S109A | >100 | <4.5 | >30 | 85 ± 11 | 7.1 ± 0.3 | 1 | N.R. | N.D. |
| 47 ± 17 | 6.7 ± 0.6 | 4 | ||||||||
N.R., no response (i.e., the measured response was not significantly different from baseline); N.D., not determined.