Predominant role of plasma membrane monoamine transporters in monoamine transport in 1321N1, a human astrocytoma-derived cell line

Fumito Naganuma, Takeo Yoshikawa, Tadaho Nakamura, Tomomitsu Iida, Ryuichi Harada, Attayeb S. Mohsen, Yamato Miura, Kazuhiko Yanai

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Monoamine neurotransmitters should be immediately removed from the synaptic cleft to avoid excessive neuronal activity. Recent studies have shown that astrocytes and neurons are involved in monoamine removal. However, the mechanism of monoamine transport by astrocytes is not entirely clear. We aimed to elucidate the transporters responsible for monoamine transport in 1321N1, a human astrocytoma-derived cell line. First, we confirmed that 1321N1 cells transported dopamine, serotonin, norepinephrine, and histamine in a time- and dose-dependent manner. Kinetics analysis suggested the involvement of low-affinity monoamine transporters, such as organic cation transporter (OCT) 2 and 3 and plasma membrane monoamine transporter (PMAT). Monoamine transport in 1321N1 cells was not Na+/Cl- dependent but was inhibited by decynium-22, an inhibitor of low-affinity monoamine transporters, which supported the importance of low-affinity transporters. RT-PCR assays revealed that 1321N1 cells expressed OCT3 and PMAT but no other neurotransmitter transporters. Another human astrocytoma-derived cell line, U251MG, and primary human astrocytes also exhibited the same gene expression pattern. Gene-knockdown assays revealed that 1321N1 and primary human astrocytes could transport monoamines predominantly through PMAT and partly through OCT3. These results might indicate that PMAT and OCT3 in human astrocytes are involved in monoamine clearance. Monoamine neurotransmitters should be immediately removed from the synaptic cleft to avoid excessive neuronal activity. Recent studies have shown that astrocytes and neurons are involved in monoamine removal. We aimed to elucidate the transporters responsible for monoamine transport by astrocytes in 1321N1, a human astrocytoma-derived cell line. Kinetics analysis suggested the involvement of low-affinity monoamine transporters, e.g., organic cation transporter (OCT) 2 and 3 and plasma membrane monoamine transporter (PMAT). Our results indicate that PMAT and OCT3 in human astrocytes are involved in monoamine clearance. Monoamine neurotransmitters should be immediately removed from the synaptic cleft to avoid excessive neuronal activity. Recent studies have shown that astrocytes and neurons are involved in monoamine removal. We aimed to elucidate the transporters responsible for monoamine transport by astrocytes in 1321N1, a human astrocytoma-derived cell line. Kinetics analysis suggested the involvement of low-affinity monoamine transporters, e.g., organic cation transporter (OCT) 2 and 3 and plasma membrane monoamine transporter (PMAT). Our results indicate that PMAT and OCT3 in human astrocytes are involved in monoamine clearance.

Original languageEnglish
Pages (from-to)591-601
Number of pages11
JournalJournal of Neurochemistry
Volume129
Issue number4
DOIs
Publication statusPublished - 2014 May

Keywords

  • astrocytes
  • low-affinity transporters
  • monoamine neurotransmitters
  • organic cation transporter
  • plasma membrane monoamine transporter

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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