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2021 Impact Factor 1.766
5-Year Impact Factor 1.674
Korean Journal of Biological Psychiatry 1994;1(1):88-97. Published online: Jan, 1, 1994
Many evidences are compatible with the correlation between the inhibition of [3H] imipramine([3H]IMI) and [3H]paroxetine([3H]PAT) binding to the 5-hydroxytryptamine(5-HT) transporter complex and the 5-HT uptake of 5-HT neurons and platelets, and most antidepressants have been shown to inhibit the [3H]IMI and [3H]PAT binding and the neuronal 5-HT uptake. However, several paradoxical research findings led to doubt about the pharmacological significance of the [3H]IMI and [3H]PAT binding sites. This study was carried to clarify the correlation between the [3H]IMI and [3H]PAT binding parameters and the tissue 5-HT content or/and [3H]5-HT uptake in the rabbit platelet, which contains 40 times ad much 5-HT as that of human platelet and shows the 10 fold higher Bmax of the 5-HT transporter binding to a 5-HT uptake inhibitor. The rabbits were treated for 28 days with amitriptyline(4mg/kg/day : AP), fluoxetine(0.5mg/kg/day : FO), and sertraline(0.5mg/kg/day : SA) via an Alzet osmotic pump implanted for constant infusion. The [3H]IMI binding Bmax and Kd of the rabbit platelets were 6.4±1.2pmol/mg protein and 10.9±2.1nM and those in the [3H]PAT binding were 8.6±1.1pmol/mg protein and 1.6±0.3nM, respectively. AP slightly increased Bmax of [3H]IMI binding and both [3H]IMI binding and [3H]PAT binding Kd, and i contrast, it slightly decreased Bmax of [3H]PAT binding. FO Slightly increased Kd of both and [3H]IMI and [3H]PAT binding and slightly decreased Bmax of [3H]IMI and [3H]PAT binding. SA produced the significant increase of [3H]PAT binding Bmax and the slight increase of both [3H]IMI and [3H]PAT binding Kd and in contrast, it slightly decreased Bmax and of [3H]IMI binding. And, the Vmax and Km of platelet [3H]5-HT uptake were 24.2±2.4pmol/108 platelets/min and 3.3±0.3nM, respectively. The Vmax was little affected by AP, FO, or SA, but the [3H]5-HT uptake Km value was moderately increased by FO. However, the platelet 5-HT content was moderately decreased by all of the 5-HT uptake inhibitors used in this study. These results seem to be consistent with the allosterical and competitive interaction of 5-HT uptake inhibiting antidepressants with each other as well as 5-HT in the 5-HT transporter binding, and provide no support for the view that the potencies of 5-HT uptake inhibitors to inhibit the [3H]IMI or [3H]PAT binding with 5-HT transporter complex correlate with their antidepressant potencies.
Keywords 5-HT Uptake inhibitors;[<sup>3</sup>H]Imipramine binding;[<sup>3</sup>H]Paroxetine binding;[<sup>3</sup>H]5-HT uptake;[<sup>3</sup>H]5-HT Content.