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Development of serotonin transporter reuptake inhibition assays using JAR cells
Decker, A. M., & Blough, B. E. (2018). Development of serotonin transporter reuptake inhibition assays using JAR cells. Journal of Pharmacological and Toxicological Methods, 92, 52-56. https://doi.org/10.1016/j.vascn.2018.03.003
INTRODUCTION: The development and validation of serotonin transporter reuptake inhibition assays in 96-well format using commercially available human placental choriocarcinoma JAR cells is described.
METHODS: JAR cells were first shown to uptake [3H]serotonin in a saturable fashion with a KMvalue of 1 μM as determined by a Michaelis-Menten kinetic analysis. The cells were then utilized to determine the reuptake inhibition potencies of known ligands and the results were compared with results previously generated in the two most commonly used transporter assays (rat brain synaptosomes and transfected HEK293 cells).
RESULTS: Examination of a variety of ligands including selective serotonin reuptake inhibitors, tricyclic antidepressants, piperazine derivatives, and phenyltropane derivatives demonstrated that JAR cells are capable of detecting reuptake inhibition activity of a variety of ligands with potencies that correlate with one or both of the other assays.
DISCUSSION: This study demonstrates a novel pharmacological method of assessing human serotonin transporter reuptake inhibition activity using commercially available JAR cells. Our results show that JAR cells provide an easily available and good alternative to using rat brain tissue and HEK293 cells, with the advantage of studying serotonin transporter reuptake inhibition in a human background.
