EC50 values for inhibition of serotonin or dopamine uptake by C. elegans VMAT in CV-1 cells
| Compound | CelVMAT SER (μm) | CelVMAT DA (μm) | HumVMAT11-a SER (μm) | HumVMAT2 SER (μm) |
|---|---|---|---|---|
| Dopamine | 0.07 (0.02–0.2)1-b | 0.04 (0.03–0.05) | 3.8 | 1.4 |
| Tyramine | 0.06 (0.01–0.2) | 0.04 (0.002–0.7) | ND | ND |
| Serotonin | 0.91 (0.26–3.2) | 0.51 (0.1–3.3)1-b | 1.4 | 0.9 |
| Norepinephrine | 2.8 (0.6–13) | 1.7 (0.3–10) | 13.7 | 3.4 |
| Octopamine | 3.4 (1.9–6.2) | 1.5 (0.1–22) | ND | ND |
| Histamine | 120 (300–1000)1-b | 117 (80–1000)1-b | 4696 | 143 |
Uptake of [3H]dopamine (DA) or [3H]serotonin (SER) was performed as described in Materials and Methods with the addition of the indicated concentration of inhibitor (as shown in Fig. 5). Assays were terminated after 4 min, except for some of the histamine data, which were collected from 15 min uptake experiments, and did not differ substantially from 4 min uptake data. Values represent calculated EC50 values for each competitor. The ranges in parenthesis represent 95% confidence limits for each EC50 value. Cel, C. elegans; Hum, human; ND, not determined.
↵F1-a The data for human VMAT1 and VMAT2 are fromErickson et al. (1996).
↵F1-b Values for which 95% confidence limits could not be obtained because of lack of convergence on 0% of control with increasing dose (when insufficient high-concentration data points were collected; see Fig. 5). In these cases, the range represents the range of concentrations invariably giving at least 80% inhibition of uptake (upper value) or no more than 20% inhibition of uptake (lower value).