Table 1.
Potency (EC50, nM) and maximum effect (% of effect of NECA) of various agonists at four signaling pathways.a
| Ligand | cAMP | Calcium | ERK1/2 | β-arrestin | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| T24 | HEK | HEK-A2B | T24 | HEK | HEK-A2B | T24 | HEK | HEK-A2b | ||
| MRS3534 | ||||||||||
| EC50 | 2160 ±350 | ND | ND | ND | ND | ND | ND | ND | ND | ND |
| Max effect | 82.0 ±5.9 | ND | ND | -0.5 ±1.7 | ND | -7.7 ±3.2 | ND | ND | ND | 10.7 ±3.2 |
| MRS3997 | ||||||||||
| EC50 | 745 ±225 | 1020 ±250 | 62.9 ±7.6 | ND | ND | ND | ND | 166 ±32 | 203 ±48 | ND |
| Max effect | 94.9 ±2.2 | 96.2 ±24.3 | 102 ±6.6 | -2.7 ±3.2 | 1.6 ±2.2 | 7.8 ±1.3 | -8.2 ±7.6 | 42.3 ±9.4 | 29.7 ±2.6 | 28.1 ±3.5 |
| MRS5911 | ||||||||||
| EC50 | 899 ±226 | 1130 ±340 | 25.3 ±7.8 | 6170 ±1990 | ND | 7150 ±2360 | ND | 1530 ±340 | 2680 ±460 | 48,100 ±13,900 |
| Max effect | 77.7 ±3.3 | 68.7 ±11.1 | 93.2 ±4.5 | 36.9 ±8.6 | 7.1 ±3.2 | 22.8 ±6.6 | 13.1 ±4.5 | 46.1 ±9.2 | 36.3 ±5.2 | 40.9 ±2.9 |
| R-PIA | ||||||||||
| EC50 | 9750 ±2840 | ND | ND | 13,100 ±4800 | ND | 14,200 ±3600 | ND | ND | ND | ND |
| Max effect | 68.6 ±7.1 | ND | ND | 9.6 ±4.1 | 0.6 ±1.4 | 18.2 ±4.9 | ND | ND | ND | 13.2 ±1.1 |
| LUF5833 | ||||||||||
| EC50 | 9.82 ±2.43 | ND | ND | NA | ND | NA | ND | ND | ND | ND |
| Max effect | 52.8 ±6.6 | ND | ND | -5.6 ±3.8 | ND | 2.8 ±2.1 | ND | ND | ND | 9.7 ±0.6 |
| BAY | ||||||||||
| EC50 | 43.0±17.7 | 296 ±146 | 6.14 ±1.61 | ND | ND | 1100 ±390 | ND | 68.8 ±4.7 | 28.9 ±4.1 | 5620 ±1240 |
| Max effect | 62.9±9.6 | 73.0 ±12.1 | 102± 1 | 2.3± 1.5 | -2.4 ±1.7 | 9.7 ±2.9 | -9.4 ±3.8 | 38.3 ±5.9 | 38.4 ±3.3 | 26.6 ±3.0 |
| CPCA | ||||||||||
| EC50 | 177 ±67 | 267 ±32 | 32.8 ±4.2 | 1930 ±680 | 2620 ±460 | 1490 ±360 | 369 ±32 | 1030 ±230 | 1860 ±240 | 5060 ±1410 |
| Max effect | 98.5 ±1.9 | 102 ±9 | 98.9 ±6.6 | 101 ±7 | 98.7 ±6.6 | 102 ±4 | 101 ±8 | 99.3 ±2.4 | 100 ±6 | 109 ±9 |
| NECA | ||||||||||
| EC50 | 242 ±72 | 331 ±146 | 21.0 ±2.5 | 1480 ±210 | 2460 ±1240 | 1850 ±450 | 478 ±66 | 787 ±168 | 2360 ±370 | 4200 ±730 |
| Max effect | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
| CGS21680 | ||||||||||
| EC50 | >10,000 | >10,000 | 2920 ±570 | ND | ND | ND | ND | ND | ND | ND |
| Max effect | -7.6 ±6.9 | 2.7 ±2.4 | 107 ±9 | -3.4±2.7 | 0.8 ±1.4 | 4.3 ±2.8 | 2.2 ±0.8 | ND | ND | ND |
| Adenosine | ||||||||||
| EC50 | 4620 ±680 | ND | ND | 11,400 ±5000 | ND | 28,400 ±5700 | ND | ND | ND | ND |
| Max effect | 97.1 ±3.8 | ND | ND | 101 ±9 | ND | 98.8 ±5.6 | ND | ND | ND | ND |
a
Results were expressed as mean±SEM from at least three independent experiments performed in duplicate or triplicate. Data related to cAMP, calcium and ERK1/2 were from assays in T24 cells and HEK293 cells expressing the human A2BAR. Data related to the β-arrestin2 translocation were from PathHunter CHO cells expressing the mouse A2BAR, as the corresponding human version did not produce a robust response.
ND, not determined or there was not a sufficient effect to determine the parameters.