Selective upregulation of Per1 mRNA expression by ATP through activation of P2X7 purinergic receptors expressed in microglial cells

Ryota Nakazato, Takeshi Takarada, Tomomi Yamamoto, Shogo Hotta, Eiichi Hinoi, Yukio Yoneda

Research output: Contribution to journalArticle

23 Citations (Scopus)


Clock genes are believed to play a pivotal role in the generation and oscillation of circadian rhythm as a central clock in the hypothalamic suprachiasmatic nucleus in the mammalian brain. In this study, mRNA expression was for the first time demonstrated with clock genes in both cultured murine microglia and microglial cell line BV-2 cells. Exposure to ATP transiently increased Period-1 (Per1) mRNA expression without affecting that of other clock genes in BV-2 cells, while a similarly transient increase was shown in Per1 mRNA expression in a manner sensitive to P2X7 purinergic receptor antagonists in cultured microglia exposed to ATP. In BV-2 cells transfected with a Per1 promoter luciferase reporter plasmid, ATP significantly increased luciferase activity in a manner sensitive to a P2X7-receptor antagonist. In both microglia and BV-2 cells, a significant increase by ATP was seen in the immunocytochemical fluorescence intensity of cells expressing Per1 protein, with mRNA expression of different P2 receptors including P2X7. Per1 siRNA significantly decreased the number of cells with processes in BV-2 cells exposed to ATP. These results suggest that ATP selectively promotes Per1 expression through gene transactivation after stimulation of P2X7 purinergic receptors in microglial cells.

Original languageEnglish
Pages (from-to)350-361
Number of pages12
JournalJournal of Pharmacological Sciences
Issue number4
Publication statusPublished - Aug 24 2011
Externally publishedYes



  • ATP
  • Clock gene
  • Microglia
  • P2X7 subtype

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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