[3H]-5-Methoxytryptoline is not actively accumulated by rabbit platelets

Summary 5-Methoxytryptoline (5-MeO-TLN, 6-methoxytetrahydro--carboline) inhibits with high affinity ³H]-imipramine binding to the serotonin transporter in platelets. To evaluate whether 5-MeO-TLN is a substrate for the serotonin transporter, the accumulation of ³H]-5-MeO-TLN into rabbit platelets was studied in vitro. At short incubation times (5 min), ³H]-5-MeO-TLN accumulation was temperature-sensitive, but not saturable over a concentration range from 0.06 mol/l to 10 mol/l Moreover, ³H]-5-MeO-TLN uptake was not affected by 100 mol/1 ouabain, its structural analogs tryptoline and 5-hydroxytryptoline, nor by the serotonin uptake inhibitors imipramine and citalopram. After longer incubation times (60 min), ³H]-5-MeO-TLN accumulation at O°C approached that seen at 37°C and temperature-sensitive ³H]-5-MeO-TLN uptake could no longer be observed. It is concluded that temperature-sensitive accumulation of ³H]-5-MeO-TLN is not mediated by the serotonin transporter and most likely represents a passive, diffusional process, the rate of which is temperature-dependent. The present studies thus confirm the hypothesis that 5-MeO-TLN affects ³H]-imipramine binding in platelets through a competitive mechanism and not via an allosteric interaction mediated through the substrate recognition site of the macromolecular complex of the serotonin transporter. Send offprint requests to S. Z. Langer at the above address