title: Antagonists and substrates differentially regulate serotonin transporter cell surface expression in serotonergic neurons.
abstract: The serotonin transporter (SERT) terminates serotonergic neurotransmission by the rapid removal of serotonin (5-hydroxytryptamine, 5-HT) from the extracellular space back into serotonergic neurons. SERT therefore controls the concentration of extracellular 5-HT, and thus one mechanism to regulate the efficacy of serotonergic neurotransmission is via modulation of the density of SERT molecules on the cell membrane. We have studied the effects of prolonged exposure to various selective serotonin re-uptake inhibitors (SSRIs), as well as cocaine and the transport substrates 5-HT and 3,4-methylenedioxy-methamphetamine (MDMA), on SERT cell surface expression in cultured serotonergic neurons. This was achieved via quantification of the amount of cell surface-expressed SERT molecules using antibody detection combined with confocal laser scanning microscopy. Our results show that exposure to the SSRIs citalopram, fluoxetine, sertraline and paroxetine all induced SERT internalization, but with different efficacies. The substrates 5-HT and MDMA also induced SERT internalization, while cocaine elevated SERT cell surface expression.
authors.affiliation: Biochemical Laboratory, Central Institute of Mental Health, J5, 68159 Mannheim, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Kittler
authors.forename: Thorsten
authors.initials: T
authors.lastname: Lau
authors.forename: Patrick
authors.initials: P
authors.lastname: Schloss
mesh_terms: D000818:Animals; D002460:Cell Line; D015283:Citalopram / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000378:metabolism / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
chemical_list: D015283:Citalopram; D003042:Cocaine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors