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Chemical and enzymatic modification of the platelet binding site for two antidepressant drugs
Author(s) -
Chudzik Jerzy,
Helmeste Daiga M.,
Tang Siu Wa
Publication year - 1992
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430270408
Subject(s) - chemistry , serotonin plasma membrane transport proteins , imipramine , paroxetine , antidepressant , serotonin , binding site , enzyme , biochemistry , serotonin transporter , pharmacology , receptor , biology , medicine , endocrinology , alternative medicine , pathology , hippocampus
Isolated human platelet membranes were subjected to chemical and enzymatic modification using a range of protein and lipid‐modifying agents. We studied the binding properties of two antidepressant drugs (imipramine and paroxetine) for the serotonin uptake protein under these conditions, with the premise that if the binding sites had different topographical requirements, then their binding properties may be differentially modulated. The results show differential modulation of binding of these two drugs by thiol/disulfide bond modifying reagents. This suggests the presence of two different mechanisms of recognition and binding for IMI and paroxetine. Additionally, the binding of both drugs to the serotonin transporter was found to be extremely sensitive to lipid‐modifying reagents, but susceptible to proteolytic cleavage only under certain environmental conditions. © 1992 Wiley‐Liss, Inc.