Interrelationship between blood serotonin levels and affinity of platelet imipramine binding sites in healthy subjects.
Changes in the density of the platelet imipramine binding sites have been reported for a variety of psychiatric conditions. The discrepancy in binding data between different laboratories renders the interpretation of the results difficult. In addition to differences in the way the various laboratories perform their binding assays, another contributing factor might be their mathematical evaluation. The imipramine binding site appears to be associated with the platelet serotonin uptake site, but it is not clear whether blood-serotonin concentrations are involved in its regulation. In order to elucidate serotonin's influence we determined blood serotonin and platelet imipramine binding simultaneously in 13 healthy female subjects. To optimize data evaluation we tested the applicability of the Scatchard analysis and a modification of the Marquardt iterative algorithm. Computer simulation of binding data suggests a superior goodness-of-fit when using the modified Marquardt algorithm. We observed a significant positive correlation between blood serotonin and the apparent dissociation constant (KD) of the imipramine binding site: the affinity decreased at high blood-serotonin concentrations (Pearson's r = 0.88, p < 0.0001). We interpret this phenomenon as serotonin's negative feedback regulation of the platelet imipramine binding site.
Meyer-Lindenberg
A
A
Department of Psychiatry Bonn, Germany.
Rao
M L
ML
D000328:Adult; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D006801:Humans; D007099:Imipramine / Q000097:blood / Q000493:pharmacokinetics*; D012701:Serotonin / Q000097:blood*
D012701:Serotonin; D007099:Imipramine