Regulation of serotonin transporter gene expression in human glial cells by growth factors.
The aims of this study were to identify monoamine transporters expressed in human glial cells, and to examine the regulation of their expression by stress-related growth factors. The expression of serotonin transporter mRNA was detected by reverse transcriptase-polymerase chain reaction in normal human astrocytes, whereas the dopamine transporter (DAT) and the norepinephrine transporter (NET) were not detected. The cDNA sequence of the "glial" serotonin transporter in astrocytes was consistent with that reported for the "neuronal" serotonin transporter (SERT). Moreover, we also demonstrated SERT expression in glial fibrillary acidic protein-positive cells by immunocytochemical staining in normal human astrocytes. Serotonin transporter gene expression was also detected in glioma-derived cell lines (A172, KG-1-C and KGK). Addition of basic fibroblast growth factor (bFGF) or epidermal growth factor (EGF) for 2 days increased serotonin transporter gene expression in astrocytes and JAR (human choriocarcinoma cell line). Basic fibroblast growth factor, but not epidermal growth factor, increased specific [3H]serotonin uptake in astrocytes in a time (1-4 days)- and concentration (20-100 ng/ml)-dependent manner. The expression of genes for basic fibroblast growth factor and epidermal growth factor receptors was detected in astrocytes. These findings suggest that the expression of the serotonin transporter in human glial cells is positively regulated by basic fibroblast growth factor.
Kubota
N
N
Department of Pharmacology, School of Medicine, Showa University, 142-8555, Tokyo, Japan.
Kiuchi
Y
Y
Nemoto
M
M
Oyamada
H
H
Ohno
M
M
Funahashi
H
H
Shioda
S
S
Oguchi
K
K
D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005910:Glioma / Q000235:genetics / Q000473:pathology; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins; D013997:Time Factors; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D006133:Growth Substances; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D016222:Fibroblast Growth Factor 2; D012701:Serotonin; D004815:Epidermal Growth Factor