Effects of nicardipine and several noscapine derivatives on the rate of ATP hydrolysis by purified, reconstituted P-glycoprotein (P-gp)
The ATPase activity of purified P-gp was measured using a colorimetric assay and plotted as a function of added drug concentration. The general dose-response relationship was fitted to the data to determine the potency to stimulate hydrolysis (EC50) and the extent of stimulation. Values correspond to mean ± S.E.M.
| Compound | (n) | Potency | Stimulation |
|---|---|---|---|
| EC50 (μM) | Fold basal | ||
| Nicardipine | (6) | 2.9 ± 0.5** | 5.3 ± 0.5 |
| Noscapine | (6) | 44.6 ± 9.1 | 3.4 ± 0.4 |
| (2) | (3) | 4.1 ± 1.6** | 2.5 ± 0.3 |
| (3) | (2) | 65.3 ± 10.2 | 4.4 ± 1.3 |
| (4) | (3) | 0.95 ± 0.28** | 2.4 ± 0.4 |
| (5) | (6) | 18.7 ± 4.5** | 3.1 ± 0.3 |
| (6) | (4) | 1.0 ± 0.4** | 1.4 ± 0.9 |
| (7) | (6) | 19.1 ± 1.4** | 2.7 ± 0.7 |
| (8) | (4) | 10.1 ± 5.3** | 2.2 ± 0.3 |
| (9) | (3) | 22.5 ± 5.8* | 2.8 ± 0.6 |
| (10) | (4) | NE | NE |
| (11) | (3) | NE | NE |
(n), Number of independent observations; NE, compound did not alter ATP hydrolysis by G-gp.
* Statistically significant difference compared with noscapine (P < 0.05).
** P < 0.01.