TABLE 4.
EC50 and Hill coefficient values (mean ± S.E.) for mutations made to the the α4β4 receptor
Mutations identified as Leu represent recovery of the wild-type receptor by nonsense suppression. Lah, α-hydroxyleucine.
| Mutation | Drug | EC50 | Hill |
|---|---|---|---|
| μm | |||
| β4L108Leu | ACh | 15.2 ± 0.9 | 1.43 ± 0.09 |
| β4L108Lah | ACh | 13 ± 2 | 1.2 ± 0.2 |
| β4L108Leu | S-Nicotine | 1.9 ± 0.2 | 1.3 ± 0.1 |
| β4L108Lah | S-Nicotine | 1.7 ± 0.2 | 1.4 ± 0.1 |
| β4L108Leu | (±)-Epibatidine | 0.0050 ± 0.0002 | 1.70 ± 0.08 |
| β4L108Lah | (±)-Epibatidine | 0.0065 ± 0.0002 | 1.71 ± 0.08 |
| β4L108Leu | Varenicline | 0.120 ± 0.004 | 1.38 ± 0.05 |
| β4L108Lah | Varenicline | 0.24 ± 0.01 | 1.19 ± 0.05 |
| β4L108Leu | (−)-Cytisine | 0.227 ± 0.005 | 1.42 ± 0.04 |
| β4L108Lah | (−)-Cytisine | 0.139 ± 0.007 | 1.40 ± 0.08 |
| β4L108Leu | Choline | 1200 ± 70 | 1.62 ± 0.09 |
| β4L108Lah | Choline | 1100 ± 100 | 1.4 ± 0.1 |
| β4L119Leu | ACh | 15.0 ± 0.7 | 1.42 ± 0.08 |
| β4L119Lah | ACh | 43 ± 4 | 1.5 ± 0.2 |
| β4L119Leu | S-Nicotine | 2.1 ± 0.2 | 1.3 ± 0.1 |
| β4L119Lah | S-Nicotine | 5.8 ± 0.4 | 1.4 ± 0.1 |
| β4L119Leu | (±)-Epibatidine | 0.0055 ± 0.0001 | 1.80 ± 0.05 |
| β4L119Lah | (±)-Epibatidine | 0.01018 ± 0.00009 | 1.63 ± 0.02 |
| β4L119Leu | Varenicline | 0.133 ± 0.002 | 1.37 ± 0.02 |
| β4L119Lah | Varenicline | 0.050 ± 0.003 | 1.5 ± 0.1 |
| β4L119Leu | (−)-Cytisine | 0.229 ± 0.004 | 1.37 ± 0.02 |
| β4L119Lah | (−)-Cytisine | 3.1 ± 0.1 | 1.37 ± 0.05 |
| β4L119Leu | Choline | 1400 ± 300 | 1.4 ± 0.2 |
| β4L119Lah | Choline | 2000 ± 700 | 1.1 ± 0.2 |