Effect of forskolin on the contractile response to oxotremorine-M in smooth muscle from wild-type and M2 muscarinic receptor KO mice
| Ileum | Trachea | Urinary Bladder | |
|---|---|---|---|
| Wild Type (n= 5) | |||
| Forskolin | |||
| E max(% control) | 90 ± 3.9 | 63 ± 5.22-a | 103 ± 2.7 |
| EC50 Shift (fold)2-b | 1.62-a | 6.72-a | 2.22-a |
| (0.20 ± 0.032) | (0.83 ± 0.057) | (0.35 ± 0.053) | |
| CEobserved 2-c | 0.572-a | 0.0982-a | 0.462-a |
| (−0.25 ± 0.033) | (−1.01 ± 0.026) | (−0.34 ± 0.058) | |
| M2 Receptor KO (n = 5) | |||
| Forskolin | |||
| Emax (% control) | 70 ± 13 | 63 ± 3.12-a | 74 ± 13 |
| EC50 Shift (fold)2-b | 4.92-a 2-d | 202-a 2-d | 162-a 2-d |
| (0.69 ± 0.055) | (1.30 ± 0.018) | (1.20 ± 0.16) | |
| CEobserved 2-c | 0.162-a 2-d | 0.0322-a 2-d | 0.0492-a 2-d |
| (−0.80 ± 0.14) | (−1.50 ± 0.029) | (−1.31 ± 0.11) |
The data were calculated from the experiments shown in Figure 1. Mean values ± S.E.M. from five wild-type and five M2receptor knockout mice are shown.
↵2-a A significant effect of the relaxant agent relative to control. The probability values for these differences are as follows. Wild-type mice, effects of forskolin:Emax in trachea, P = 0.0020; EC50 shift in ileum, trachea, and urinary bladder,P = 0.0079, 0.00013, and 0.0028; CEobservedin ileum, trachea, and urinary bladder, P = 0.0023, 7.0 × 10−9, and 0.0012. M2muscarinic receptor knockout mice, effects of forskolin:Emax in trachea, P = 0.00030; EC50 shift in ileum, trachea, and urinary bladder,P = 0.0011, 2.1 × 10−7, and 0.0016; CEobserved in ileum, trachea, and urinary bladder,P = 0.00046, 1.8 × 10−10, and 1.3 × 10−7.
↵2-b Denotes the EC50 value of oxotremorine-M measured in the presence of the relaxant agent divided by that measured in its absence. The values in parentheses beneath each estimate represent the mean log EC50 shift values ± S.E.M.
↵2-c Denotes the observed coupling efficiency of oxotremorine-M in the presence of the relaxant agent relative to that in the absence of the relaxant agent. The values in parentheses beneath each estimate represent the mean log CEobservedvalues ± S.E.M.
↵2-d Significantly different from the relaxant effect observed in wild-type mice. The probability values for these differences are as follows. Effects of forskolin on EC50shift in ileum, trachea, and urinary bladder, P = 0.00027, 0.000047, and 0.0021; effects of forskolin on CEobserved in ileum, trachea, and urinary bladder,P = 0.00090, 2.9 × 10−6, and 0.00086.