title: Serotonin transporter in lymphocytes of rats exposed to physical restraint stress.
abstract: OBJECTIVE
  Glucocorticoids and stress cause transcriptional and functional changes on the serotonin transporter (SERT) in the central nervous system. Stress can produce specific modifications of SERT in lymphocytes, which could be associated with alterations in immune response. The aim of this study was to evaluate the effect of a physical restraint stress protocol on (1) rat lymphocyte proliferation in the presence of the selective serotonin reuptake inhibitor fluoxetine and (2) SERT kinetic parameters, i.e. binding capacity (Bmax), affinity (Kd) and Hill coefficient (nH).
  
  
  METHODS
  Male adult Sprague-Dawley rats were placed in Plexiglass boxes (5 h daily for 5 days), and blood was obtained by cardiac puncture on day 6. Serum corticosterone was quantitated by an immunoenzymatic assay. Lymphocytes were isolated by density gradients and adhesion to plastic, of which there was sufficient material for further experiments, then cultured with or without the mitogen concanavalin A (Con A, 2 μg/ml) and fluoxetine (1-50 μM). Cell proliferation was measured with tetrazolium salts, and [(3)H]paroxetine was used as a SERT-specific ligand for binding assays.
  
  
  RESULTS
  Restraint produced a significant increase in serum corticosterone of stressed rats. The proliferative response to Con A was similar in the controls and stressed animals. Fluoxetine reduced cell proliferation with and without Con A. Restraint diminished the inhibitory effect of fluoxetine on proliferation. Restraint also increased Bmax and Kd, but decreased nH. Treatment of rats with actinomycin D, a transcription inhibitor, reduced Bmax in stressed animals.
  
  
  CONCLUSIONS
  Restraint stress modulated the effect of fluoxetine on cell proliferation, probably through the modification of the presence and the function of SERT.
authors.affiliation: Laboratorio de Neuroquímica, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.
authors.forename: Matilde
authors.initials: M
authors.lastname: Medina-Martel
authors.forename: Mary
authors.initials: M
authors.lastname: Urbina
authors.forename: Fili
authors.initials: F
authors.lastname: Fazzino
authors.forename: Lucimey
authors.initials: L
authors.lastname: Lima
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D050486:Serotonin Plasma Membrane Transport Proteins / Q000032:analysis / Q000096:biosynthesis*; D013315:Stress, Psychological / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat