Human plasma inhibitors of platelet serotonin uptake and imipramine receptor binding: extraction and heterogeneity.
Human plasma contains a considerable concentration of low molecular weight substances that inhibit, in a dose-dependent manner, both high-affinity imipramine receptor binding and serotonin uptake in platelets. Incubation of plasma with alumina was used to extract and to partly characterize these imipramine-like inhibitors. The human plasma extract inhibited imipramine binding and serotonin uptake with median inhibitory concentration (IC50) of 0.18 +/- 0.1 and 0.36 +/- 0.15 mg/ml, respectively. Imipramine-like activity of the extract was markedly degraded by carboxypeptidase B and leucine aminopeptidase, but was resistant to neurominidase and phospholipases A2, C, and D. The elution profile of the extract after gel chromatography on Bio-Gel P-2 showed two major peaks of serotonin uptake and imipramine binding inhibition and three additional peaks of serotonin uptake inhibitory activity that did not have a significant effect on imipramine binding. The possible mechanism of pharmacological action of the imipramine-like inhibitors and their relation to development of affective illnesses remain to be clarified.
Brusov
O S
OS
Fomenko
A M
AM
Katasonov
A B
AB
D001792:Blood Platelets / Q000378:metabolism*; D002352:Carrier Proteins; D002850:Chromatography, Gel; D003866:Depressive Disorder / Q000097:blood; D006801:Humans; D007099:Imipramine / Q000037:antagonists & inhibitors* / Q000097:blood; D007700:Kinetics; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D012701:Serotonin / Q000097:blood; D012702:Serotonin Antagonists / Q000097:blood*
D002352:Carrier Proteins; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter; D012702:Serotonin Antagonists; C027775:imipramine receptor; D012701:Serotonin; D007099:Imipramine