High- and low-affinity [3H]imipramine binding sites on human platelets: separate determination and involvement of sulphur-containing bonds

Demushkin, V. P.; Fomenko, Andrey M.; Plyashkevich, Yury G.; Shchurin, M. R.; Os, Brusov

doi:10.1016/0014-2999(87)90802-8

Cited by 7 publications

(2 citation statements)

References 31 publications

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“…21,24], Several attempts to clarify the discrepancies have been made and method ological aspects have been pointed out. Although the possible influence of the heterogeneity of the binding site on [3H]-imipramine platelet binding has already been mentioned [17,20], the concentrations of [3H]-imipramine used in most of the previous reports are often high (over 5 nM), enough to make possible its binding to the low-affinity site [13,17]. Here, the classic Scatchard analysis is inappropriate to determine the Bmax of highaffinity binding and can lead to erroneous data.…”

Section: Discussionmentioning

confidence: 97%

“…We focused our attention on the low-affinity [3H]-imipramine binding site present at the platelet level [13,17,30,34] and its possible influence on the quantitative estimates of high-affinity bindings, depending both on the range of the ligand concentration and on the experi mental data analysis used. When concentrations of la belled imipramine over 5 nM were used, the saturation isotherm of the specific binding was not asymptotic to the horizontal, and the Bmax of the high-affinity site, if estimated as usual by Scatchard graphic analysis, is over valued.…”

Section: Introductionmentioning

confidence: 99%

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Platelet [<sup>3</sup>H]-Imipramine Binding according to DSM-III Subtypes of Depression

Jeanningros¹,

Gronier²,

Azorin³

et al. 1989

Neuropsychobiology

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The question of the previously reported changes in the density of high-affinity binding sites for [³H]-imipramine (IMI) in platelets from depressed patients was reexamined among the different diagnostic subtypes of depression according to the DSM-III classification and taking into account the possible influence of the low-affinity binding site. Using a least-square computer-assisted analysis, a precise determination of the [³H]-IMI binding parameters exclusively in relationship to the high-affinity site was performed in 46 untreated depressed patients and compared to 35 healthy controls. The results revealed a clear and highly significant 22% decrease in the maximal density (B_max) of [³H]-IMI binding in all of the depressed patients compared to controls with no change in affinity values. Considering the diagnostic subgroups, we found that all the bipolar patients, the depressed as well as the euthymic or manic ones, had very low B_max values and that some of them also exhibited an unusual low-affinity binding. Mean B_max of the unipolar and dysthymic patients significantly decreased when compared to controls, although the B_max values showed a large variability. Only dysthymic patients presented B_max values which were significantly associated to symptom severity as assessed by the Hamilton Depression Rating Scale scores. Our results confirm the lower density of platelet [³H]-IMI binding in affective disorders, particularly in bipolar patients, and also suggest that this biological parameter is a trait marker in bipolar depression and a state marker in dysthmic disorder.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Platelet [<sup>3</sup>H]-Imipramine Binding according to DSM-III Subtypes of Depression

Jeanningros¹,

Gronier²,

Azorin³

et al. 1989

Neuropsychobiology

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Platelet 5-HT uptake sites in depression: three concurrent measures using [3H] imipramine and [3H] paroxetine

et al. 1993

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Platelet 5-HT uptake sites were measured in 40 depressed patients and 40 controls using [3H] imipramine binding, defined with desmethylimipramine (DMI) and Na+ dependence, and [3H] paroxetine binding. In control subjects the Bmax of DMI defined [3H] imipramine binding was significantly higher than both Na+ dependent [3H] imipramine (by 30%) and [3H] paroxetine binding (by 22%). The Bmax of Na+ dependent [3H] imipramine and [3H] paroxetine binding did not differ significantly. The Kd of Na+ dependent [3H] imipramine binding was significantly lower than the Kd of DMI defined [3H] imipramine binding. The binding of DMI defined and Na+ dependent [3H] imipramine and [3H] paroxetine did not differ significantly between depressed patients and controls in the total group, in those depressed patients and controls in the total group, in those depressed patients who had never taken antidepressants or in those depressed patients who had been recently withdrawn from antidepressants. This study provides no support for the view that the number of platelet 5-HT uptake sites are reduced in depression.

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Differences between sodium-dependent and desipramine-defined [3H]imipramine binding in intact human platelets

Hrdina

1989

Biological Psychiatry

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High- and low-affinity [3H]imipramine binding sites on human platelets: separate determination and involvement of sulphur-containing bonds

Cited by 7 publications

References 31 publications

Platelet [<sup>3</sup>H]-Imipramine Binding according to DSM-III Subtypes of Depression

Platelet [<sup>3</sup>H]-Imipramine Binding according to DSM-III Subtypes of Depression

Platelet 5-HT uptake sites in depression: three concurrent measures using [3H] imipramine and [3H] paroxetine

Differences between sodium-dependent and desipramine-defined [3H]imipramine binding in intact human platelets

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