Table 8 Parameters of functional response of M4_G15 fusion protein to muscarinic agonists.

From: Applications and limitations of fitting of the operational model to determine relative efficacies of agonists

 

pEC50

E’MAX

pKA

τ

[35S]GTPγS binding, EMAX = 6.85

Arecoline

6.98 ± 0.03

4.2 ± 0.2

6.6 ± 0.1

1.60 ± 0.12

Carbachol

6.94 ± 0.03

4.3 ± 0.2

6.5 ± 0.1

1.74 ± 0.13

Furmethide

6.58 ± 0.03

4.4 ± 0.2

6.1 ± 0.1

1.77 ± 0.13

Iperoxo

7.88 ± 0.02

5.0 ± 0.3

7.3 ± 0.1

2.70 ± 0.22

McN-A-343

6.86 ± 0.03

4.0 ± 0.2

6.5 ± 0.1

1.43 ± 0.12

NDMC

7.01 ± 0.03

3.9 ± 0.2

6.6 ± 0.1

1.32 ± 0.11

Oxotremorine

7.77 ± 0.02

4.4 ± 0.2

7.3 ± 0.1

1.84 ± 0.13

Pilocarpine

6.78 ± 0.03

3.0 ± 0.2

6.5 ± 0.1

0.80 ± 0.06

Xanomeline

8.50 ± 0.02

4.6 ± 0.2

8.0 ± 0.1

2.06 ± 0.16

IPX level, EMAX = 4.18

Arecoline

7.10 ± 0.02

2.9 ± 0.1

6.6 ± 0.1

2.37 ± 0.22

Carbachol

7.02 ± 0.03

3.0 ± 0.2

6.5 ± 0.1

2.45 ± 0.23

Furmethide

6.67 ± 0.03

3.0 ± 0.2

6.1 ± 0.1

2.57 ± 0.25

Iperoxo

7.97 ± 0.02

3.3 ± 0.2

7.3 ± 0.1

3.9 ± 0.4

McN-A-343

6.92 ± 0.03

2.8 ± 0.1

6.5 ± 0.1

1.96 ± 0.18

NDMC

7.10 ± 0.03

2.7 ± 0.1

6.7 ± 0.1

1.79 ± 0.16

Oxotremorine

7.82 ± 0.02

3.0 ± 0.2

7.3 ± 0.1

2.48 ± 0.24

Pilocarpine

6.85 ± 0.02

2.2 ± 0.1

6.5 ± 0.1

1.08 ± 0.09

Xanomeline

8.62 ± 0.02

3.1 ± 0.2

8.0 ± 0.1

2.77 ± 0.28

Intracellular Ca2+ level, EMAX = 1.861

Arecoline

8.32 ± 0.02

1.828 ± 0.003

6.6 ± 0.1

57 ± 10

Carbachol

8.22 ± 0.03

1.829 ± 0.003

6.4 ± 0.1

59 ± 10

Furmethide

7.93 ± 0.03

1.830 ± 0.003

6.1 ± 0.1

61 ± 11

Iperoxo

9.27 ± 0.02

1.839 ± 0.003

7.3 ± 0.1

87 ± 29

McN-A-343

8.08 ± 0.03

1.820 ± 0.003

6.4 ± 0.1

45 ± 5

NDMC

8.24 ± 0.03

1.816 ± 0.003

6.6 ± 0.1

41 ± 6

Oxotremorine

9.05 ± 0.02

1.831 ± 0.003

7.2 ± 0.1

63 ± 11

Pilocarpine

8.00 ± 0.02

1.791 ± 0.003

6.6 ± 0.1

26 ± 4

Xanomeline

9.93 ± 0.02

1.834 ± 0.003

8.1 ± 0.1

71 ± 14

  1. Equation (10) was fitted to individual data sets. Equation (6) was fitted to E’MAX versus EC50 data from all 3 experiments for all agonists to obtain EMAX of the assay. Equation (1) with fixed EMAX was fitted to individual functional responses. Data are means ± SD from 3 independent experiments.
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