Abstract
The serotonin transporter expressed in brain, platelets, and placenta is a primary target for antidepressants, cocaine, and amphetamines. Here we report that interleukin-1 beta is a potent regulator of the expression of this transporter. The activity of the serotonin transporter in human JAR choriocarcinoma cells is stimulated by this cytokine and the stimulation is accompanied by an increase in the steady state levels of the transporter mRNAs and in the transporter density. The increase in mRNA levels is effectively blocked by actinomycin D. The stimulatory effect of interleukin-1 beta is not associated with any change in the cellular levels of cAMP, indicating involvement of a cAMP-independent pathway. Even though cholera toxin, which is known to increase cAMP levels, also upregulates the serotonin transporter in JAR cells, the effects of interleukin-1 beta and cholera toxin on the transporter activity are additive. This constitutes the first report on the identification of a physiologically occurring hormone/cytokine which upregulates the expression of the human serotonin transporter gene.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Biological Transport / drug effects
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Carrier Proteins / biosynthesis*
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Cell Line
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Cell Membrane / metabolism
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Choriocarcinoma
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Cocaine / analogs & derivatives
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Cocaine / metabolism
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Cyclic AMP / metabolism
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Cyclic GMP / metabolism
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Cycloheximide / pharmacology
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Dactinomycin / pharmacology
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Dose-Response Relationship, Drug
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Female
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Gene Expression Regulation, Neoplastic / drug effects*
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Humans
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Imipramine / pharmacology
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Interleukin-1 / pharmacology*
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Iodine Radioisotopes
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Kinetics
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Membrane Glycoproteins / biosynthesis*
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Membrane Transport Proteins*
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Nerve Tissue Proteins*
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Pregnancy
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RNA, Messenger / biosynthesis
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RNA, Messenger / metabolism
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Serotonin / metabolism
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Serotonin Plasma Membrane Transport Proteins
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Time Factors
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Tumor Cells, Cultured
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Uterine Neoplasms
Substances
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Carrier Proteins
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Interleukin-1
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Iodine Radioisotopes
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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RNA, Messenger
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SLC6A4 protein, human
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Serotonin Plasma Membrane Transport Proteins
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Dactinomycin
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Serotonin
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2beta-carbomethoxy-3beta-(4-iodophenyl)tropane
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Cycloheximide
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Cyclic AMP
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Cyclic GMP
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Cocaine
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Imipramine