Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Biochem Pharmacol
2007 Jan 01;731:147-54. doi: 10.1016/j.bcp.2006.09.008.
Show Gene links
Show Anatomy links
Evidence for significant contribution of a newly identified monoamine transporter (PMAT) to serotonin uptake in the human brain.
Zhou M
,
Engel K
,
Wang J
.
???displayArticle.abstract???
The high affinity serotonin transporter (SERT) constitutes the principal pathway for removal of serotonin (5-HT) from extracellular fluid of brain, but evidence indicates that other transporters may also be involved in this process. We recently reported the cloning of a novel plasma membrane monoamine transporter (PMAT), which is abundantly expressed in the human brain and avidly transports 5-HT [Engel K, Zhou M, Wang J. Identification and characterization of a novel monoamine transporter in the human brain. J Biol Chem 2004;279:50042-9]. In this study, we evaluated whether PMAT contributes to total human brain uptake of 5-HT using a hybrid depletion approach in Xenopus laevis oocytes. We also examined whether PMAT interacts with selective serotonin reuptake inhibitors (SSRIs) using MDCK cells stably expressing recombinant human PMAT. Microinjection of total human brain poly(A)(+) mRNA into oocytes elicited approximately 2.5-3-fold increase in 5-HT uptake. Pre-hybridization of poly(A)(+) mRNA with PMAT or SERT antisense oligonucleotides significantly reduced mRNA-induced 5-HT uptake. An additive inhibitory effect was observed when poly(A)(+) mRNA was co-hybridized with both PMAT and SERT antisense oligonucleotides. In contrast, mRNA-induced 5-HT uptake was not affected by pre-hybridization with sense oligonucleotides. These data suggest that functional transcripts of PMAT are present in the human brain, and the PMAT transporter may be significantly involved in brain uptake of 5-HT. All five tested SSRIs inhibited PMAT with IC(50) values ranging from 11 to 116 microM, which are much greater than clinically encountered concentrations, suggesting that PMAT activity is minimally affected by SSRI therapies.
Austin,
Expression of serotonin transporter messenger RNA in the human brain.
1994, Pubmed
Austin,
Expression of serotonin transporter messenger RNA in the human brain.
1994,
Pubmed
Barker,
High affinity recognition of serotonin transporter antagonists defined by species-scanning mutagenesis. An aromatic residue in transmembrane domain I dictates species-selective recognition of citalopram and mazindol.
1998,
Pubmed
Baumann,
Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors.
1996,
Pubmed
Bengel,
Altered brain serotonin homeostasis and locomotor insensitivity to 3, 4-methylenedioxymethamphetamine ("Ecstasy") in serotonin transporter-deficient mice.
1998,
Pubmed
Blakely,
Molecular physiology of norepinephrine and serotonin transporters.
1994,
Pubmed
Carlsson,
Perspectives on the discovery of central monoaminergic neurotransmission.
1987,
Pubmed
DeVane,
Metabolism and pharmacokinetics of selective serotonin reuptake inhibitors.
1999,
Pubmed
Eisenhofer,
The role of neuronal and extraneuronal plasma membrane transporters in the inactivation of peripheral catecholamines.
2001,
Pubmed
Engel,
Identification and characterization of a novel monoamine transporter in the human brain.
2004,
Pubmed
,
Xenbase
Engel,
Interaction of organic cations with a newly identified plasma membrane monoamine transporter.
2005,
Pubmed
Feng,
Local inhibition of organic cation transporters increases extracellular serotonin in the medial hypothalamus.
2005,
Pubmed
Gainetdinov,
Monoamine transporters: from genes to behavior.
2003,
Pubmed
Greengard,
The neurobiology of slow synaptic transmission.
2001,
Pubmed
Hagenbuch,
Effect of antisense oligonucleotides on the expression of hepatocellular bile acid and organic anion uptake systems in Xenopus laevis oocytes.
1996,
Pubmed
,
Xenbase
Liu,
Evaluation of cerebrospinal fluid concentration and plasma free concentration as a surrogate measurement for brain free concentration.
2006,
Pubmed
Magagnin,
Poly(A)+ RNA from rabbit intestinal mucosa induces b0,+ and y+ amino acid transport activities in Xenopus laevis oocytes.
1992,
Pubmed
,
Xenbase
Miyamoto,
Relative contributions of Na+-dependent phosphate co-transporters to phosphate transport in mouse kidney: RNase H-mediated hybrid depletion analysis.
1997,
Pubmed
,
Xenbase
Nakai,
Human liver-specific organic anion transporter, LST-1, mediates uptake of pravastatin by human hepatocytes.
2001,
Pubmed
,
Xenbase
Pan,
Plasticity in serotonin uptake in primary neuronal cultures of serotonin transporter knockout mice.
2001,
Pubmed
Ramamoorthy,
Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization.
1993,
Pubmed
Ravary,
Abnormal trafficking and subcellular localization of an N-terminally truncated serotonin transporter protein.
2001,
Pubmed
Reyes-Haro,
Uptake of serotonin by adult rat corpus callosum is partially reduced by common antidepressants.
2003,
Pubmed
Rosenthal,
Targeting cell surface receptors with ligand-conjugated nanocrystals.
2002,
Pubmed
,
Xenbase
Schildkraut,
Toward a rapidly acting antidepressant: the normetanephrine and extraneuronal monoamine transporter (uptake 2) hypothesis.
2004,
Pubmed
Schömig,
The extraneuronal monoamine transporter exists in human central nervous system glia.
1998,
Pubmed
Shaskan,
Kinetics of serotonin accumulation into slices from rat brain: relationship to catecholamine uptake.
1970,
Pubmed
Thakker,
siRNA-mediated knockdown of the serotonin transporter in the adult mouse brain.
2005,
Pubmed
Torres,
Plasma membrane monoamine transporters: structure, regulation and function.
2003,
Pubmed
White,
Serotonin transporters: implications for antidepressant drug development.
2005,
Pubmed
Wu,
Identity of the organic cation transporter OCT3 as the extraneuronal monoamine transporter (uptake2) and evidence for the expression of the transporter in the brain.
1998,
Pubmed
,
Xenbase
You,
Molecular characteristics of Na(+)-coupled glucose transporters in adult and embryonic rat kidney.
1995,
Pubmed
,
Xenbase
Youdim,
The therapeutic potential of monoamine oxidase inhibitors.
2006,
Pubmed