pKi and Ki values of NET substrates and inhibitors for inhibition of norepinephrine uptake in COS-7 cells expressing the rat, human, or bovine NET
| Compound | n | pKiValue ± S.E.M. (with Ki value in parentheses) | ||
|---|---|---|---|---|
| Rat NET | Human NET | Bovine NET | ||
| Substrate | ||||
| Dopamine | 3 | 6.406 ± 0.065 | 6.492 ± 0.061 | 6.401 ± 0.055 |
| (392 nM) | (323 nM) | (397 nM) | ||
| MPP+ | 4 | 6.109 ± 0.030 | 6.295 ± 0.0302-a | 6.244 ± 0.032 |
| (778 nM) | (507 nM) | (570 nM) | ||
| (−)-Epinephrine | 4 | 5.187 ± 0.040 | 5.435 ± 0.0342-c | 5.301 ± 0.0332-c 2-d |
| (6.50 μM) | (3.68 μM) | (5.00 μM) | ||
| Inhibitor | ||||
| Nisoxetine | 4 | 8.241 ± 0.049 | 8.376 ± 0.122 | 8.221 ± 0.082 |
| (5.74 nM) | (4.21 nM) | (6.01 nM) | ||
| Desipramine | 3 | 8.133 ± 0.091 | 8.069 ± 0.046 | 8.052 ± 0.023 |
| (7.36 nM) | (8.54 nM) | (8.88 nM) | ||
| Imipramine | 4 | 7.085 ± 0.080 | 6.929 ± 0.047 | 7.029 ± 0.063 |
| (82.2 nM) | (118 nM) | (93.6 nM) | ||
| Cocaine | 4 | 6.400 ± 0.037 | 6.664 ± 0.0872-a | 6.702 ± 0.0492-b |
| (398 nM) | (217 nM) | (197 nM) | ||
IC50 values were calculated from percent inhibition of specific uptake of [3H]norepinephrine (10 nM, 2 min) data from each ofn experiments. Each IC50 value was converted into aKi value according to the Cheng and Prusoff method assuming competitive inhibition (Cheng and Prusoff, 1973). Values are shown as pKi values ± S.E.M. (with the meanKi value in parentheses) from nexperiments. Data were analyzed by one-factor repeated measures ANOVA (because each experiment included rat, human, and bovine NETs for a particular substrate or inhibitor), followed by post-hoc ttests when the ANOVA showed a significant variation in the pKivalues.