Evidence for the existence of serotonin uptake inhibitor-like substances in human cerebrospinal fluid.
Addition of human cerebrospinal fluid (CSF) induced a marked inhibition of 3H-paroxetine binding to the monkey cortical membranes, while the specific binding of 3H-imipramine was slightly inhibited. Moreover, 3H-serotonin (5-hydroxy-tryptamine, 5-HT) uptake inhibition in the monkey cortical synaptosomes was also increased as the volume of added CSF was increased. Scatchard analysis of specific 3H-paroxetine binding with human CSF showed non-competitive kinetics, although CSF was competitive with 3H-imipramine binding. The inhibitory effect of human CSF on 5-HT uptake was non-competitive in nature. The endogenous substances in human CSF most probably act at the recognition site labeled with 3H-paroxetine. Moreover, occupation of this site by the endogenous substances is likely to inhibit the 5-HT uptake process.
Goto
S
S
Department of Pharmacology, Medical College of Oita, Japan.
Egashira
T
T
Yamanaka
Y
Y
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D000882:Haplorhini; D006801:Humans; D007099:Imipramine / Q000378:metabolism; D017374:Paroxetine; D010880:Piperidines / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000134:cerebrospinal fluid*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D010880:Piperidines; D012702:Serotonin Antagonists; D012701:Serotonin; D017374:Paroxetine; D007099:Imipramine