TABLE 2.
Kinetic parameters describing interactions of PfCRTDd2 with chloroquine, quinine, and verapamil
Shown are the best-fit values of kinetic parameters obtained using the full and partial mixed-type inhibition models. The drug present in radiolabeled form was denoted as the substrate, and the unlabeled drug was denoted as the inhibitor. CI, confidence interval; Vmax, the maximum velocity of substrate transport; KSCQ, KSQN, and KSVP, the dissociation constants for the chloroquine-PfCRTDd2, quinine-PfCRTDd2, and verapamil-PfCRTDd2 complexes, respectively; α, the factor by which these KS values change when the opposing substrate is already bound to the transporter; β, the factor by which the Vmax is affected by the inhibitor; CQ, chloroquine; QN, quinine; VP, verapamil.
| Substrate | Inhibitor | Parameters | Mixed (full) |
Mixed (partial) |
||
|---|---|---|---|---|---|---|
| Mean ± S.E. | 95% CI | Mean ± S.E. | 95% CI | |||
| CQ | QN | Vmax (pmol/oocyte/h) | 33 ± 2 | 29–37 | 33 ± 2 | 29–37 |
| KSCQ (μm) | 250 ± 30 | 192–315 | 250 ± 30 | 192–316 | ||
| KSQN (μm) | 40 ± 7 | 26–54 | 40 ± 7 | 25–53 | ||
| α | 2.6 ± 1 | 0.3–5 | 2.6 ± 1 | 0.3–5 | ||
| β | 0.02 ± 0.03 | −0.04–0.1 | ||||
| QN | CQ | Vmax (pmol/oocyte/h) | 9 ± 0.2 | 9–10 | 9 ± 0.2 | 9–10 |
| KSQN (μm) | 25 ± 1 | 22–28 | 25 ± 1 | 22–28 | ||
| KSCQ (μm) | 340 ± 50 | 240–440 | 342 ± 54 | 234–450 | ||
| α | 1.9 ± 0.5 | 0.9–2.8 | 2 ± 0.5 | 0.9–2.8 | ||
| β | 0.00 ± 0.03 | −0.05–0.05 | ||||
| CQ | VP | Vmax (pmol/oocyte/h) | 27 ± 0.3 | 26–27 | 27 ± 0.3 | 26–27 |
| KSCQ (μm) | 195 ± 6 | 183–208 | 196 ± 6 | 185–207 | ||
| KSVP (μm) | 36 ± 2 | 32–40 | 35 ± 2 | 31–38 | ||
| α | 2.9 ± 0.4 | 2–4 | 3 ± 0.3 | 2–3 | ||
| β | 0.03 ± 0.01 | 0.01–0.05 | ||||