Antagonist potencies at ferret α4β2 and at the high-sensitivity form expressed from UTR-containing α4(u) and β2(u)
Concentration-inhibition curves projected to 100% inhibition for methyllycaconitine, mecamylamine, d-tubocurarine, and chlorisondamine, but not for DHβE. For DHβE acting on α4β2 the projected maximal inhibition was 80 ± 3% with 2 μM acetylcholine and 95 ± 4% with 200 μM acetylcholine, whereas these values at α4(u)β2(u) were 90 ± 2% with 2 μM acetylcholine and 84 ± 3% with 200 μM acetylcholine.
| Antagonist | α4β2 | α4(u)β2(u) | ||||
|---|---|---|---|---|---|---|
| IC50 | nH | n | IC50 | nH | n | |
| μM | μM | |||||
| 2 μM Acetylcholine | ||||||
| DHβE | 0.0023 (0.0010-0.0050) | 0.83 ± 0.20 | 3 | 0.0027 (0.0020-0.0036) | 1.20 ± 0.18 | 3 |
| MLA | 0.063 (0.049-0.081) | 1.29 ± 0.18 | 3 | 0.13 (0.11-0.16) | 1.52 ± 0.18 | 3 |
| Mecamylamine | 0.58 (0.27-1.26) | 0.65 ± 0.14 | 3 | 2.0 (1.2-3.3) | 0.72 ± 0.12 | 3 |
| d-Tubocurarine | 110 (11-1200) | 0.41 ± 0.30 | 3 | 4.7 (3.2-7.0) | 0.78 ± 0.11 | 4 |
| Chlorisondamine | 0.52 (0.34-0.80) | 0.63 ± 0.08 | 5 | 18 (13-26) | 1.00 ± 0.16 | 5 |
| 200 μM Acetylcholine | ||||||
| DHβE | 0.0056 (0.0021-0.015) | 0.60 ± 0.15 | 3 | 0.0036 (0.0020-0.0062) | 0.95 ± 0.21 | 3 |
| MLA | 0.038 (0.032-0.045) | 1.23 ± 0.11 | 3 | 0.101 (0.073-0.139) | 1.23 ± 0.21 | 3 |
| Mecamylamine | 0.24 (0.21-0.28) | 0.90 ± 0.05 | 6 | 3.81 (2.67-5.64) | 1.10 ± 0.21 | 6 |
| d-Tubocurarine | 0.92 (0.69-1.23) | 0.75 ± 0.07 | 5 | 49.7 (8.8-280) | 0.39 ± 0.13 | 3 |
| Chlorisondamine | 0.18 (0.17-0.20) | 1.14 ± 0.05 | 6 | 3.3 (2.9-3.7) | 0.84 ± 0.03 | 2 |