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Allosteric Interaction Between the Site Labeled by [ 3 H]Imipramine and the Serotonin Transporter in Human Platelets
Author(s) -
Meyerson Laurence R.,
Ieni John R.,
Wennogle Lawrence P.
Publication year - 1987
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.1471-4159.1987.tb04129.x
Subject(s) - imipramine , chemistry , serotonin plasma membrane transport proteins , platelet , binding site , serotonin transporter , serotonin , allosteric regulation , chlorpromazine , transporter , pharmacology , biochemistry , medicine , receptor , biology , alternative medicine , pathology , gene
The nature of interaction between the site labeled by [ 3 H]imipramine (IMI) and the 5‐hydroxytryptamine (5‐HT, serotonin) transporter in human platelets was examined. The sulfhydryl characterizing agent N ‐ethylmaleimide (NEM) differentially affected [ 3 H]5‐HT uptake and [ 3 H]IMI binding in human platelet preparations. Concentrations of NEM that completely abolished [ 3 H]5‐HT uptake only minimally reduced [ 3 H]IMI binding. Examining the effect of IMI on the kinetics of human platelet [ 3 H]5‐HT uptake revealed significant reductions in maximal velocity ( V max ) without altering affinity ( K m ). IC 50 values for selected uptake blockers on [ 3 H]IMI binding and [ 3 H]5‐HT uptake were determined. IC 50 values of these compounds for uptake and binding revealed that agents such as IMI, chlorpromazine, amitriptyline, and nisoxetine were preferential inhibitors of [ 3 H]IMI binding whereas fluoxetine, CL 216,303, pyril‐amine, and bicifadine were preferential [ 3 H]5‐HT uptake blockers. 5‐HT was a weak displacer of [ 3 H]IMI binding (IC 25 = 3.0 μ M ) and exhibited a rather low Hill coefficient (n H app = 0.46). Results reported herein support the notion of an allosteric interaction between the [ 3 H]IMI binding site and the 5‐HT transporter complex in human platelets.