Serotonin transporter modulation in blood lymphocytes from patients with major depression.
1. Serotonin is a neurotransmitter in the central nervous system which has been implicated in the aetiology and pathogenesis of affective disorders. The serononergic system also plays several roles in the immune system through the expression of a number of its receptor subtypes in the immune cells. 2. Following release serotonin is inactivated by reuptake into neurons and other cells by a specific serotonin sodium and chloride-dependent transporter molecule, whose structure has been elucidated. 3. Measurement [3H]paroxetine binding showed that human lymphocytes contain a high-affinity serotonin transporter. 4. To assess the serotonin function in major depression, we investigated serotonin transporter density in blood lymphocytes from patients with this disorder and selected according to the interview of the American Psychiatric Association. 5. Patients were divided into two groups and treated with two different antidepressant drugs, one group receiving fluoxetine, a selective serotonin reuptake inhibitor, and another mirtazapine, an antagonist of alpha2-adrenergic auto and heteroreceptors, for a period of 6 weeks. 6. Blood samples were obtained before and after the treatment, lymphocytes were isolated by Ficoll/Hypaque gradient, subjected to differential adhesion to plastic, and cell membranes were prepared for binding assay of [3H]paroxetine. 7. Lymphocytes serotonin transporter number was significantly reduced, while the affinity was unchanged, in patients with major depression disorder as compare to controls. 8. In addition, there was a partial recovery in lymphocytes serotonin (5HT) transporter number in the period posterior to the antidepressants administration, accompanied with clinical and depression rating scales improvement. Serotonin was determined in platelet-poor plasma and in lymphocytes before and after drugs administration, showing a significant decrease in the patients treated compared to untreated and controls. 9. These results are evidence of the potential interaction between the nervous and immune systems. The mechanisms underlying this interaction are under study, and might be related to modifications in the expression or function of the serotonin transporters in lymphocytes of depressed patients.
Lima
Lucimey
L
Laboratorio de Neuroquímica, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela. llima@cbb.ivic.ve
Urbina
Mary
M
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000328:Adult; D018687:Antidepressive Agents, Second-Generation; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000097:blood* / Q000188:drug therapy / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008803:Mianserin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000078785:Mirtazapine; D009419:Nerve Tissue Proteins; D015213:Neuroimmunomodulation / Q000502:physiology*; D017374:Paroxetine; D011869:Radioligand Assay; D012701:Serotonin / Q000097:blood*; D050486:Serotonin Plasma Membrane Transport Proteins; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D018687:Antidepressive Agents, Second-Generation; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D005473:Fluoxetine; D008803:Mianserin; D012701:Serotonin; D017374:Paroxetine; D000078785:Mirtazapine