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Tryptamine, a Substrate for the Serotonin Transporter in Human Platelets, Modifies the Dissociation Kinetics of [ 3 H]Imipramine Binding: Possible Allosteric Interaction
Author(s) -
Segonzac A.,
Raisman R.,
Tateishi T.,
Schoemaker H.,
Hicks P. E.,
Langer S. Z.
Publication year - 1985
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1985.tb05423.x
Subject(s) - tryptamine , imipramine , serotonin transporter , serotonin , serotonin plasma membrane transport proteins , chemistry , allosteric regulation , 5 ht receptor , tricyclic , pharmacology , stereochemistry , biochemistry , biophysics , receptor , biology , medicine , alternative medicine , pathology
Tricyclic antidepressants and nontricyclic serotonin (5‐hydroxytryptamine) uptake blockers monophasically inhibit [ 3 H]imipramine binding in human platelets. Similarly, serotonin and tryptamine inhibit the binding of [ 3 H]imipramine in the low micromolar range and with a pseudo‐Hill coefficient near unity. Dissociation of the [ 3 H]imipramine receptor complex in the presence of uptake inhibitors follows first‐order kinetics with a half‐life of approximately 60 min. Although serotonin and tryptamine do not decrease [ 3 H]imipramine binding when added under equilibrium conditions, simultaneous addition of serotonin or tryptamine with serotonin uptake inhibitors decreases the rate of ligand‐receptor dissociation in a concentration‐dependent manner. These data suggest a common site of action for serotonin, which is the substrate of the transporter system, and of tryptamine, its nonhydroxylated analog. This hypothesis is supported by the identification of a high‐affinity ( K m = 0.55 μ M ), saturable, and temperature‐dependent uptake of [ 3 H]tryptamine in human platelets. Uptake of [ 3 H]tryptamine was inhibited potently by imipramine and nontricyclic serotonin uptake inhibitors with a potency similar to that observed for [ 3 H]serotonin uptake. These data support the hypothesis that in platelets, [ 3 H]imipramine, tricyclic, and nontricyclic serotonin up‐take inhibitors bind to a common recognition site that is associated with the serotonin transporter but that differs from the substrate recognition site of the carrier through which serotonin and tryptamine exert a heterotropic allosteric modulation on [ 3 H]imipramine binding.