Cimaterol Log EC50 | % Isoprenaline | n | Log KB CGP20712A | n | Log KB ICI118551 | n | Log KB propranolol | n | Log KB CGP12177 | n | |
---|---|---|---|---|---|---|---|---|---|---|---|
Cimaterol as agonist: stable mixed populations of cells | |||||||||||
β1-WT | −8.29 ± 0.04 | 81.2 ± 2.1 | 24 | −9.36 ± 0.07 | 35 | −7.13 ± 0.06 | 31 | −8.69 ± 0.08 | 30 | −10.01 ± 0.06 | 33 |
β1-A187G | −8.22 ± 0.08 | 78.9 ± 2.3 | 8 | −9.23 ± 0.08 | 14 | −7.02 ± 0.07 | 8 | −8.72 ± 0.09 | 8 | −9.99 ± 0.06 | 17 |
β1-V189T | −8.20 ± 0.04 | 80.6 ± 1.8 | 12 | −9.26 ± 0.09 | 20 | −7.73 ± 0.07* | 15 | −8.61 ± 0.05 | 14 | −9.81 ± 0.08 | 27 |
β1-L195Q | −8.20 ± 0.05 | 80.6 ± 2.7 | 12 | −8.97 ± 0.10 | 19 | −7.12 ± 0.07 | 15 | −8.86 ± 0.11 | 14 | −9.85 ± 0.07 | 25 |
β1-W199Y | −8.46 ± 0.06 | 77.3 ± 2.4 | 12 | −9.66 ± 0.08 | 19 | −7.39 ± 0.07 | 16 | −9.01 ± 0.12 | 15 | −10.06 ± 0.05 | 26 |
β1-W199A | −8.63 ± 0.07* | 85.4 ± 3.2 | 8 | −9.51 ± 0.14 | 13 | −7.26 ± 0.08 | 11 | −9.12 ± 0.11 | 13 | −10.07 ± 0.16 | 4 |
β1-W199D | −8.91 ± 0.07* | 87.6 ± 3.5 | 8 | −9.88 ± 0.08 | 12 | −7.48 ± 0.11 | 10 | −9.17 ± 0.10 | 12 | −9.85 ± 0.12 | 8 |
β1-W199F | −8.71 ± 0.09* | 80.0 ± 2.6 | 8 | −10.14 ± 0.10* | 14 | −7.19 ± 0.12 | 12 | −9.09 ± 0.13 | 14 | −9.95 ± 0.16 | 11 |
β1-W199K | −7.64 ± 0.05* | 86.4 ± 3.2 | 8 | −9.46 ± 0.08 | 14 | −6.41 ± 0.06* | 9 | −8.00 ± 0.12* | 10 | a | |
β1-W199L | −7.60 ± 0.06* | 75.2 ± 2.9 | 8 | −10.06 ± 0.11* | 12 | −6.90 ± 0.11 | 11 | −8.72 ± 0.06 | 12 | a | |
β1-W199N | −8.88 ± 0.06* | 84.6 ± 5.4 | 8 | −9.93 ± 0.09 | 11 | −7.21 ± 0.08 | 12 | −9.22 ± 0.10 | 13 | −10.12 ± 0.12 | 12 |
β1-V189T-L195Q | −8.22 ± 0.04 | 87.0 ± 3.4 | 8 | −9.49 ± 0.09 | 13 | −7.67 ± 0.10* | 11 | −8.81 ± 0.11 | 14 | −9.58 ± 0.09 | 12 |
β1-V189T-W199Y | −8.62 ± 0.07* | 84.2 ± 2.1 | 8 | −9.93 ± 0.08 | 12 | −7.85 ± 0.08* | 10 | −8.80 ± 0.08 | 12 | −10.10 ± 0.15 | 11 |
β1-L195Q-W199Y | −8.41 ± 0.06 | 79.6 ± 2.0 | 8 | −9.68 ± 0.06 | 13 | −7.24 ± 0.06 | 11 | −9.04 ± 0.11 | 12 | −9.82 ± 0.14 | 9 |
β1-V189T-L195Q-W199Y | −8.44 ± 0.04 | 82.7 ± 2.7 | 8 | −9.85 ± 0.08 | 14 | −7.92 ± 0.06* | 11 | −8.99 ± 0.09 | 14 | −9.79 ± 0.11 | 12 |
β1-TM4 | −8.32 ± 0.05 | 77.3 ± 1.9 | 23 | −9.43 ± 0.09 | 35 | −7.94 ± 0.06* | 31 | −9.08 ± 0.07 | 29 | −9.98 ± 0.09 | 35 |
CGP12177 Log EC50 | % Isoprenaline | n | Log KB CGP20712A | n | Log KB ICI118551 | n | Log KB propranolol | n | |||
CGP12177 as agonist: stable mixed populations of cells | |||||||||||
β1-WT | −8.12 ± 0.07 | 53.3 ± 1.5 | 21 | −7.37 ± 0.08 | 37 | −5.86 ± 0.08 | 22 | −6.69 ± 0.08 | 27 | ||
β1-A187G | −8.21 ± 0.09 | 41.5 ± 3.1 | 7 | −7.25 ± 0.11 | 12 | −5.81 ± 0.08 | 7 | −6.72 ± 0.12 | 10 | ||
β1-V189T | −8.01 ± 0.07 | 44.1 ± 2.3 | 11 | −7.64 ± 0.08 | 21 | −6.36 ± 0.09* | 16 | −6.98 ± 0.08 | 24 | ||
β1-L195Q | −9.00 ± 0.06* | 32.9 ± 1.4* | 11 | −8.53 ± 0.09* | 19 | −6.64 ± 0.11* | 13 | −7.74 ± 0.12* | 21 | ||
β1-W199Y | −9.16 ± 0.05* | 40.2 ± 2.3* | 11 | −8.46 ± 0.07* | 23 | −6.69 ± 0.09* | 17 | −7.90 ± 0.09* | 29 | ||
β1-W199A | −9.46 ± 0.11* | 68.6 ± 4.0* | 8 | −8.79 ± 0.10* | 12 | −6.88 ± 0.11* | 9 | −7.96 ± 0.15* | 9 | ||
β1-W199D | −9.48 ± 0.08* | 45.3 ± 3.3 | 8 | −8.94 ± 0.09* | 17 | −6.98 ± 0.16* | 13 | −8.87 ± 0.12* | 20 | ||
β1-W199F | −8.95 ± 0.13* | 58.6 ± 3.4 | 8 | −8.10 ± 0.07* | 13 | −6.53 ± 0.10* | 10 | −7.61 ± 0.17* | 12 | ||
β1-W199K | −9.40 ± 0.05* | 85.1 ± 2.5* | 8 | −8.13 ± 0.10* | 18 | −6.34 ± 0.09* | 13 | −7.47 ± 0.08* | 20 | ||
β1-W199L | −9.20 ± 0.06* | 82.9 ± 3.2* | 8 | −8.12 ± 0.09* | 20 | −6.45 ± 0.08* | 13 | −7.56 ± 0.11* | 20 | ||
β1-W199N | −9.27 ± 0.12* | 47.7 ± 3.2 | 8 | −8.26 ± 0.11* | 12 | −6.67 ± 0.10* | 10 | −8.19 ± 0.09* | 17 | ||
β1-V189T-L195Q | −9.21 ± 0.06* | 35.1 ± 2.6* | 8 | −8.64 ± 0.09* | 15 | −7.11 ± 0.08* | 12 | −8.17 ± 0.10* | 14 | ||
β1-V189T-W199Y | −9.07 ± 0.11* | 43.2 ± 2.9 | 8 | −8.70 ± 0.08* | 18 | −7.42 ± 0.14* | 13 | −7.82 ± 0.10* | 16 | ||
β1-L195Q-W199Y | −9.51 ± 0.06* | 41.3 ± 2.3 | 8 | −9.17 ± 0.12* | 15 | −6.94 ± 0.09* | 12 | −8.15 ± 0.11* | 15 | ||
β1-V189T-L195Q-W199Y | −9.40 ± 0.07* | 39.2 ± 2.4* | 8 | −9.21 ± 0.12* | 14 | −7.49 ± 0.07* | 12 | −8.66 ± 0.11* | 16 | ||
β1-TM4 | −9.43 ± 0.06* | 33.9 ± 1.5* | 19 | −8.98 ± 0.07* | 39 | −7.64 ± 0.08* | 32 | −8.39 ± 0.06* | 40 |
↵a CGP12177 is very efficacious in these mutants, similar to cimaterol, and it is therefore not possible to measure a log KB value for CGP12177 by a rightward shift of the cimaterol concentration response.
↵* P < 0.001 One-way ANOVA with post hoc Newman–Keuls comparing values from the mutant receptors with those obtained from the β1-WT, thus the log KB for ICI118551 at β1-V189T is different from that obtained from the β1-WT with P < 0.001