TABLE 3

Coupling efficiency (logτC) parameters of ligands at M4 mAChR constructs

Values represent the mean ± S.E.M. from at least three separate experiments performed in triplicate. LogτCC) is the logarithm of the corrected operational efficacy parameter, τC, determined via nonlinear regression of the concentration-response data to an operational model of agonism; antilogarithms are shown in parentheses.

LogτCC)
AChPilocarpineLY2033298McN-A-343NDMC
M4 WT2.09 ± 0.09 (123)−0.93 ± 0.08 (0.1)1.37 ± 0.08 (23)0.84 ± 0.17 (7)N.R.
M4 D1063.26A0.60 ± 0.22* (4)N.R.N.R.N.R.N.R.
M4 W1083.28A1.77 ± 0.11 (59)N.R.N.R.N.R.N.R.
M4 L1093.29A1.23 ± 0.11* (17)N.R.N.R.N.R.N.R.
M4 D1123.32NN.R.N.R.N.R.N.R.N.R.
M4 D1123.32E−1.20 ± 0.74* (0.06)N.R.N.R.N.R.N.R.
M4 S1163.36A1.19 ± 0.15* (15)N.R.0.02 ± 0.11* (1)N.R.N.R.
M4 N1173.37A1.14 ± 0.09* (14)N.R.−0.19 ± 0.19* (0.7)−0.93 ± 0.19* (0.1)N.R.
M4 V1203.40A1.50 ± 0.13* (32)0.33 ± 0.10* (2)0.88 ± 0.12* (8)0.01 ± 0.19* (1)−0.85 ± 0.26 (0.1)
M4 D1293.49E1.29 ± 0.20* (19)N.R.0.72 ± 0.18* (5)0.43 ± 0.37 (3)N.R.
M4 D1293.49N2.38 ± 0.15 (240)0.45 ± 0.27* (3)1.34 ± 0.14 (22)1.87 ± 0.21* (74)0.19 ± 0.14 (2)
  • N.R., no response.

  • * p < 0.05, significantly different from WT value as determined by one-way ANOVA with Dunnett's post hoc test.