Further studies on the endogenous serotonin-uptake-inhibitor-like substances in the human cerebrospinal fluid.
The properties of endogenous substances that inhibit 5HT uptake in human cerebrospinal fluid (CSF) were investigated. Human CSF was loaded onto a Sephadex G-25 column, and each fraction was tested for its ability to inhibit [3H]paroxetine binding in monkey brain preparations. We found four different inhibitory peaks with respective molecular weights (M.W.) of > 12400, 2000 and two of < 1350. The third and fourth peaks (F-3, F-4: < 1350 M.W.) of inhibitory activity were determined to consist of some monoamines (5HT, etc.) or their metabolites (5HIAA, etc.) and other unidentified compounds by using an HPLC-electrochemical detector. The second peak (F-2, M.W. about 2000) displaced [3H]paroxetine binding noncompetitively (decreased Bmax and did not change Kd) and inhibited [3H]5HT uptake noncompetitively (decreased Vmax and did not change Km), but had no effect on either [3H]norepinephrine uptake or [3H]dopamine uptake. These results suggest that the endogenous substances that selectively inhibit 5HT uptake are present in human CSF as low molecular weight compounds.
Goto
S
S
Department of Pharmacology, Oita Medical University, Japan.
Egashira
T
T
Yamanaka
Y
Y
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D000882:Haplorhini; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008970:Molecular Weight; D009638:Norepinephrine / Q000378:metabolism; D017374:Paroxetine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000134:cerebrospinal fluid* / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D004298:Dopamine; D006897:Hydroxyindoleacetic Acid; D009638:Norepinephrine; D017374:Paroxetine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors