PMID- 20006597 OWN - NLM STAT- MEDLINE DCOM- 20100330 LR - 20221207 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 629 IP - 1-3 DP - 2010 Mar 10 TI - Antagonists and substrates differentially regulate serotonin transporter cell surface expression in serotonergic neurons. PG - 63-7 LID - 10.1016/j.ejphar.2009.12.010 [doi] AB - 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. CI - Copyright (c) 2009 Elsevier B.V. All rights reserved. FAU - Kittler, Katharina AU - Kittler K AD - Biochemical Laboratory, Central Institute of Mental Health, J5, 68159 Mannheim, Germany. FAU - Lau, Thorsten AU - Lau T FAU - Schloss, Patrick AU - Schloss P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091216 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Serotonin Plasma Membrane Transport Proteins) RN - 0 (Serotonin Uptake Inhibitors) RN - 0DHU5B8D6V (Citalopram) RN - 333DO1RDJY (Serotonin) RN - I5Y540LHVR (Cocaine) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Animals MH - Cell Line MH - Citalopram/pharmacology MH - Cocaine/pharmacology MH - Gene Expression Regulation/*drug effects MH - N-Methyl-3,4-methylenedioxyamphetamine/metabolism/pharmacology MH - Neurons/cytology/*drug effects/*metabolism MH - Protein Transport/drug effects MH - Serotonin/*metabolism/pharmacology MH - Serotonin Plasma Membrane Transport Proteins/*metabolism MH - Selective Serotonin Reuptake Inhibitors/*pharmacology EDAT- 2009/12/17 06:00 MHDA- 2010/03/31 06:00 CRDT- 2009/12/17 06:00 PHST- 2009/10/19 00:00 [received] PHST- 2009/11/19 00:00 [revised] PHST- 2009/12/07 00:00 [accepted] PHST- 2009/12/17 06:00 [entrez] PHST- 2009/12/17 06:00 [pubmed] PHST- 2010/03/31 06:00 [medline] AID - S0014-2999(09)01131-5 [pii] AID - 10.1016/j.ejphar.2009.12.010 [doi] PST - ppublish SO - Eur J Pharmacol. 2010 Mar 10;629(1-3):63-7. doi: 10.1016/j.ejphar.2009.12.010. Epub 2009 Dec 16.