Regulation of ethanol-sensitive EAAT2 expression through adenosine A1 receptor in astrocytes

Jinhua Wu, Moonnoh R. Lee, Taehyun Kim, Sandy Johng, Suzanne Rohrback, Nayoung Kang, Doo Sup Choi

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Adenosine-regulated glutamate signaling in astrocytes is implicated in many neurological and neuropsychiatric disorders. In this study, we examined whether adenosine A1 receptor regulates EAAT2 expression in astrocytes using pharmacological agents and siRNAs. We found that adenosine A1 receptor-specific antagonist DPCPX or PSB36 decreased EAAT2 expression in a dose-dependent manner. Consistently, knockdown of A1 receptor in astrocytes decreased EAAT2 mRNA expression while overexpression of A1 receptor upregulated EAAT2 expression and function. Since A1 receptor activation is mainly coupled to inhibitory G-proteins and inhibits the activity of adenylate cyclase, we investigated the effect of forskolin, which activates adenylate cyclase activity, on EAAT2 mRNA levels. Interestingly, we found that forskolin reduced EAAT2 expression in dose- and time-dependent manners. In contrast, adenylate cyclase inhibitor SQ22536 increased EAAT2 expression in dose- and time-dependent manners. In addition, forskolin blocked ethanol-induced EAAT2 upregulation. Taken together, these results suggest that A1 receptor-mediated signaling regulates EAAT2 expression in astrocytes.

Original languageEnglish (US)
Pages (from-to)47-52
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume406
Issue number1
DOIs
StatePublished - Mar 4 2011

Keywords

  • Adenosine A1 receptor
  • Adenylate cyclase
  • Alcoholisms
  • Astrocytes
  • EAAT2
  • Glutamate

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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