title: Serotonin uptake is largely mediated by platelets versus lymphocytes in peripheral blood cells.
abstract: The serotonin transporter (SERT), a primary target for many antidepressants, is expressed in the brain and also in peripheral blood cells. Although platelet SERT function is well accepted, lymphocyte SERT function has not been definitively characterized. Due to their small size, platelets often are found in peripheral blood mononuclear cell preparations aimed at isolating lymphocytes, monocytes, and macrophages. The presence of different cells makes it difficult to assign SERT expression and function to specific cell types. Here, we use flow cytometry and IDT307, a monoamine transporter substrate that fluoresces after uptake into cells, to investigate SERT function in lymphocyte and platelet populations independently, as well as simultaneously without prior isolation. We find that murine lymphocytes exhibit temperature-dependent IDT307 transport but uptake is independent of SERT. Lack of measurable SERT function in lymphocytes was corroborated by chronoamperometry using serotonin as a substrate. When we examined rhesus and human mixed blood cell populations, we found that platelets, and not lymphocytes, were primary contributors to SERT function. Overall, these findings indicate that lymphocyte SERT function is minimal. Moreover, flow cytometry, in conjunction with the fluorescent transporter substrate IDT307, can be widely applied to investigate SERT in platelets from populations of clinical significance.
authors: Semel Institute for Neuroscience & Human Behavior and Hatos Center for Neuropharmacology, David Geffen School of Medicine, University of California, Los Angeles, California, United States.
authors: Brendan S
authors: BS
authors: Beikmann
authors: Ian D
authors: ID
authors: Tomlinson
authors: Sandra J
authors: SJ
authors: Rosenthal
authors: Anne Milasincic
authors: AM
authors: Andrews
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D005453:Fluorescence; D057809:HEK293 Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D051379:Mice; D012701:Serotonin / Q000493:pharmacokinetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D050493:Vesicular Monoamine Transport Proteins / Q000494:pharmacology
chemical_list: D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D050493:Vesicular Monoamine Transport Proteins