Gain-of-function multiple combinatorial mutations in gAT1Areceptors
| Receptor | Ang II | Losartan | ||
|---|---|---|---|---|
| EC50 | Fmut | EC50 | Fmut | |
| nM | nM | |||
| Wild-type | ||||
| hAT1 | 4.5 ± 0.6 | 1.0 | 15 ± 2.4 | 1.0 |
| gAT1A | 5.4 ± 1.2 | 1.2 | 5900 ± 870 | 393 |
| gAT1A variants: gain-of-function | ||||
| G107S/I108V/V150I/V151I | 3.9 ± 0.3 | 0.9 | 16 ± 3.0 | 1.1 |
| G107S/I108V/S177I | 4.0 ± 0.2 | 0.9 | 25 ± 2.4 | 1.7 |
| G107S/I108V/V150I/V151I/S177I | 4.2 ± 0.4 | 0.9 | 29 ± 4.1 | 1.9 |
| G107S/I108V/V150I/V151I/S177I/V83L | 6.1 ± 0.3 | 1.4 | 40 ± 3.7 | 2.7 |
| V150I/V151I/S177I | 3.3 ± 0.6 | 0.7 | 2750 ± 340 | 183 |
| V150I/V151I/S177I/V83L | 4.7 ± 0.7 | 1.0 | 8300 ± 990 | 553 |
Data are the mean ± S.E.M. obtained from two to four experiments (each done in triplicate) after displacement of125I-Sar1-Ang II binding. by increasing concentrations of losartan, for selected gAT1A mutant receptors transfected to COS-7 cells. To makeF mut values comparable, theF mut values of each mutant used the human EC50 value as a control for comparison.
F mut, mutant EC50/hAT1 EC50.