Human plasma inhibitors of platelet serotonin uptake and imipramine receptor binding: Extraction and heterogeneity

Os, Brusov; Fomenko, Andrey M.; Katasonov, A.B.

doi:10.1016/0006-3223(85)90053-8

Cited by 43 publications

(7 citation statements)

References 21 publications

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“…This hypothesis is supported by the reports of the extraction from brain tissue of a substance having the properties of a ligand for the [3H]-IMI recognition site (Barbaccia et al 1983;Rehavi et al 1985). It is of interest that endogenous factors, present in human plasma extracts, inhibit both [3H]-5HT uptake (Angel and Paul 1984) and [3H]-IMI binding (Brusov et al 1985). The identification of this endocoid acting on the [3H]-IMI recognition site to modulate serotonin uptake would be of considerable interest in studies on the pathophysiology of depression.…”

Section: Discussionmentioning

confidence: 80%

“…Recently, several laboratories have proposed the existence of an endogenous inhibitor of the [3H]-IMI binding site, different from 5HT, which could subserve the function of an endogenous modulator of 5HT uptake (Langer et al 1984b;Barbaccia et al 1983;Rehavi et al 1985;Angel and Paul 1984;Segonzac et al 1985;Brusov et al 1985). It is tempting to speculate that a change in the circulating concentration of this endocoid could be responsible for the modification of the parameters of [3H]-IMI binding and the decreased Bma x observed in platelets of patients during a depressive episode.…”

Section: Discussionmentioning

confidence: 99%

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Reduced Bmax of [3H]-imipramine binding to platelets of depressed patients free of previous medication with 5HT uptake inhibitors

et al. 1986

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The high-affinity binding sites for [3H]-imipramine (IMI) present in human platelets are associated with the neuronal uptake system for 5HT. It was recently demonstrated that previous antidepressant therapy with drugs which inhibit 5HT uptake could down-regulate [3H]-IMI binding and that this effect could persist up to 1 month after the end of treatment. We therefore re-examined the reported differences in Bmax of [3H]-IMI binding in platelets between control and depressed untreated patients, to evaluate the residual influence of previous antidepressant medication. The saturation characteristics of [3H]-IMI binding were compared in platelets from 17 depressed patients carefully selected according to previous antidepressant therapy and washout period, who were closely matched, for age and sex, with a group of control healthy volunteers. The results reveal a significant decrease by 47% in the Bmax of [3H]-IMI binding in platelets of untreated depressed patients when compared with controls. There was no significant modification of Kd values for platelet [3H]-IMI binding between the depressed and the control groups. Our results support the view that platelet [3H]-IMI binding is a useful tool as a biological marker in depression.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Reduced Bmax of [3H]-imipramine binding to platelets of depressed patients free of previous medication with 5HT uptake inhibitors

et al. 1986

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“…Recently, it has been reported that [3H]imipramine binding sites and [3H]paroxetine binding sites that regulate 5-hydroxytryptamine (5HT) up take are modulated by unidentified endogenous sub stance(s) in human plasma (2)(3)(4)(5) and in rat brain and plas ma (6 9 (13,14). In this study we report more detailed investiga tions of the properties of the selective 5HT uptake inhibi tor-like substances in human CSF.…”

mentioning

confidence: 99%

Further Studies on the Endogenous Serotonin-Uptake-Inhibitor-Like Substances in the Human Cerebrospinal Fluid

Goto

Egashira

Yamanaka

1993

Japanese Journal of Pharmacology

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ABSTRACT-Theproperties 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 us ing an HPLC-electrochemical detector. (13, 14). In this study we report more detailed investiga tions of the properties of the selective 5HT uptake inhibi tor-like substances in human CSF. MATERIALS AND METHODSMonkeys were anesthetized with ketaral (30 mg/kg, s.c.), and their brains were quickly removed after withdrawing blood. Fifty milliliters of human CSF sam ples were obtained from 25 patients in the course of rou tine diagnostic lumbar puncture and were collected in the Central Laboratory of Medicine. The monkey brains and the pooled human CSF were stored at -80°C until used. Gel filtrationFive milliliters of evaporated human CSF sample was chromatographed in a Sephadex G-25 column (1.9 x 87 cm) with 1 mM phosphate buffer, pH 7.4, at a flow rate of 103 ml/hr, and effluent fractions of 5.15 ml/tube were col lected. Column effluents were monitored by measuring ab sorbances at 280 nm. Aliquots (100µl) of each fraction were assayed for the ability to displace [3H]paroxetine binding. The molecular weights (M.W.s) of endogenous 5HT-uptake-inhibitor-like substances were estimated by chromatography in the same column calibrated with mark ers of known M.W. Paroxetine binding assay (15)Monkey frontal cortices were homogenized in 25 vol. of ice-cold 50 mM Tris-HC1 buffer (containing 100 mM NaCI and 5 mM KCI, pH 7.4). The P2 fractions obtained by centrifugation of this homogenate were used as the crude membrane preparations (final concentration of ap proximately 0.1 mg protein/tube) for the assay. Aliquots of crude membrane suspension were incubated with[3H]paroxetine at 221C at a final volume of 250,u1 for 180 min. Fluoxetine at 10,uM final concentration was used to determine non-specific binding. The incubation was termi nated by rapid filtration of the membrane suspension un der reduced pressure through Whatman GF/B glass fiber filters. Each filter was rapidly washed three times with 5 ml of ice-cold 50 mM Tris-HC1 buffer, pH 7.4. The filters were then dried and the radioactivities were determined in Triton X-100-toluene scintillation fluid in a liquid scintilla tion spectrometer. Monoamine uptake assay The study of [3H]5HT, [3H]norepinephrine (NE) or[3H]dopamine (DA) uptake into synaptosomes was con ducted according to the method of Snyder and Coyle (16), but with minor modifications. The monkey brains (bilateral frontal cortex) were homogenized in 0.32M sucrose, and the crude synaptosomes were obtained by different...

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“…One previous study also has shown a dose-dependent inhibition of platelet 5-HT uptake following the addition of human plasma extracts (Brusov et al, 1985). However, that study used plasma only from normal subjects.…”

Section: Discussionmentioning

confidence: 94%

“…Recent evidence has indicated that brain and plasma contain factors that affect 5-HT uptake in platelets (Brusov et al, 1985) and brain synaptosomes (Rehavi et al, 1985). Alteration of the plasma concentration or activity of one or more of these endogenous factors may be responsible for the changes in platelet 5-HT mechanisms observed in patients with PMS.…”

Section: Introductionmentioning

confidence: 99%

Alteration of 5-HT uptake by plasma fractions in the premenstrual syndrome

Ashby

Carr

Cook

et al. 1990

J. Neural Transmission

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The effects of plasma and an aqueous plasma fraction from patients with premenstrual syndrome (PMS) and control subjects on the uptake of 5-hydroxytryptamine (5-HT) in washed human platelets and rat forebrain synaptosomes were studied. Pre- and postmenstrual samples of unextracted plasma from the control group significantly enhanced platelet uptake of 5-HT. In contrast, an aqueous fraction following extraction of the plasma with organic solvents caused a dose-dependent decrease of 5-HT uptake. Plasma obtained from patients with PMS caused less stimulation of 5-HT uptake compared to plasma from the control group. The aqueous fraction of premenstrual plasma from patients tended to inhibit 5-HT uptake to a greater extent than a similar plasma fraction from controls. The inhibition of 5-HT uptake was associated with an increase in Km. Aqueous plasma fractions from both groups also inhibited 5-HT uptake in brain synaptosomes. However, there were no significant differences between groups. The results of the platelet study suggest that there may be quantitative differences in the plasma concentration of endogenous factors that affect 5-HT uptake between patients with PMS and control subjects and that such differences may explain the previously reported alteration of platelet 5-HT uptake and content associated with PMS symptoms.

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Human plasma inhibitors of platelet serotonin uptake and imipramine receptor binding: Extraction and heterogeneity

Cited by 43 publications

References 21 publications

Reduced Bmax of [3H]-imipramine binding to platelets of depressed patients free of previous medication with 5HT uptake inhibitors

Reduced Bmax of [3H]-imipramine binding to platelets of depressed patients free of previous medication with 5HT uptake inhibitors

Further Studies on the Endogenous Serotonin-Uptake-Inhibitor-Like Substances in the Human Cerebrospinal Fluid

Alteration of 5-HT uptake by plasma fractions in the premenstrual syndrome

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