TABLE 3.
GnRH-elicited IP responses at wild-type and mutant human GnRH receptors
IP responses (pEC50) were determined in COS-7 cells transfected with wild-type and mutant receptors. Maximum IP responses (Emax) were expressed relative to wild-type controls in each transfection. Values are mean ± S.E. of three or more independent experiments, converted to nm (in parentheses).
| Mutant | GnRH I |
GnRH II |
||
|---|---|---|---|---|
| pEC50 | Emax | pEC50 | Emax | |
| (nm) | % WT | (nm) | % WT | |
| WT | 8.77 ± 0.11 (1.7) | 100 | 7.70 ± 0.07 (20.1) | 100 |
| WT + NBI-42902a | 8.74 ± 0.08 (1.8) | 86 ± 10 | 7.69 ± 0.04 (20.4) | 92 ± 7 |
| P173A | 7.39 ± 0.17 (41.2) | 79 ± 8 | 6.10 ± 0.12 (787) | 82 ± 10 |
| Q174A | 7.56 ± 0.18 (27.7) | 81 ± 4 | 6.33 ± 0.12 (464) | 90 ± 1 |
| L175A + NBI-42902a | 8.41 ± 0.06 (3.9) | 60 ± 8 | 7.66 ± 0.04 (22.1) | 59 ± 7 |
| Y176A | 7.82 ± 0.11 (15.0) | 37 ± 3 | 6.81 ± 0.01 (153) | 31 ± 7 |
| I177A | 8.50 ± 0.34 (3.1) | 17 ± 4 | 7.02 ± 0.12 (94.6) | 17 ± 8 |
| F178A | 6.41 ± 0.10 (386) | 105 ± 23 | 4.71 ± 0.24 (19400) | 103 ± 79 |
| F178L + NBI-42902a | 6.86 ± 0.11 (139) | 82 ± 18 | 5.44 ± 0.16 (3640) | 46 ± 15 |
| F178W | 8.30 ± 0.26 (5.1) | 46 ± 8 | 6.86 ± 0.25 (138) | 39 ± 15 |
| R179A + NBI-42902a | 8.53 ± 0.15 (3.0) | 59 ± 4 | 7.05 ± 0.17 (90.2) | 45 ± 14 |
| M180A | 7.79 ± 0.08 (16.4) | 82 ± 2 | 7.35 ± 0.14 (45.1) | 70 ± 21 |
a Pretreated with NBI-42902.