RESUMO
The serotonin transporter (5-HTT) plays a critical role in the termination of serotonin neurotransmission and represents the prime target for selective serotonin reuptake inhibitors (SSRIs). In the present study, the 5-HTT protein in human peripheral blood lymphocyte was characterized pharmacologically and biochemically. The tricyclic antidepressant drug [(3)H]imipramine, an established ligand for the neuronal and platelet 5-HTT, bound saturably and reversibly to a single population of non-interacting binding sites in fresh human peripheral blood lymphocytes. The affinity of [(3)H]imipramine (K(d)) to the transporter, calculated from association and dissociation kinetic experiments, was similar to that obtained from the equilibrium study. The function of the transporter was studied using high affinity [(3)H]5-HT uptake into fresh lymphocytes. [(3)H]Imipramine binding and [(3)H]5-HT uptake were inhibited by tricyclic antidepressants as well as by SSRIs. Western blot analysis as well as immunoprecipitation analysis revealed labeling of a single protein band of approximately 100 kDa. The presence of the 5-HTT in easily accessible nucleated cells such as peripheral blood lymphocytes might permit molecular genetic studies in mood and anxiety disorder patients, and might enhance the understanding of the different efficacies of antidepressants in depressed patients.