[3H]-5-methoxytryptoline is not actively accumulated by rabbit platelets.
5-Methoxytryptoline (5-MeO-TLN, 6-methoxytetrahydro-beta-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 mumol/l to 10 mumol/l. Moreover, [3H]-5-MeO-TLN uptake was not affected by 100 mumol/l 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 0 degree C approached that seen at 37 degrees 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 serotonin transporter.
D000818:Animals; D001692:Biological Transport; D001792:Blood Platelets / Q000378:metabolism*; D002243:Carbolines / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D007099:Imipramine / Q000097:blood; D066298:In Vitro Techniques; D007700:Kinetics; D011817:Rabbits; D012701:Serotonin / Q000097:blood; D012964:Sodium / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature; D014363:Tryptamines / Q000097:blood
D002243:Carbolines; D014363:Tryptamines; C045647:5-methoxytryptoline; D012701:Serotonin; D012964:Sodium; D007099:Imipramine