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

23 Citations (Scopus)

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

Fingerprint

Adenosine A1 Receptors
Astrocytes
Colforsin
Ethanol
Adenylyl Cyclases
Adenosine A1 Receptor Antagonists
Messenger RNA
Nervous System Diseases
GTP-Binding Proteins
Adenosine
Glutamic Acid
Up-Regulation
Chemical activation
Pharmacology

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Regulation of ethanol-sensitive EAAT2 expression through adenosine A1 receptor in astrocytes. / Wu, Jinhua; Lee, Moonnoh R.; Kim, Taehyun; Johng, Sandy; Rohrback, Suzanne; Kang, Nayoung; Choi, Doo Sup.

In: Biochemical and Biophysical Research Communications, Vol. 406, No. 1, 04.03.2011, p. 47-52.

Research output: Contribution to journalArticle

Wu, Jinhua ; Lee, Moonnoh R. ; Kim, Taehyun ; Johng, Sandy ; Rohrback, Suzanne ; Kang, Nayoung ; Choi, Doo Sup. / Regulation of ethanol-sensitive EAAT2 expression through adenosine A1 receptor in astrocytes. In: Biochemical and Biophysical Research Communications. 2011 ; Vol. 406, No. 1. pp. 47-52.
@article{7ab70ba2eb8641ad956c1d4b72fddcb6,
title = "Regulation of ethanol-sensitive EAAT2 expression through adenosine A1 receptor in astrocytes",
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.",
keywords = "Adenosine A1 receptor, Adenylate cyclase, Alcoholisms, Astrocytes, EAAT2, Glutamate",
author = "Jinhua Wu and Lee, {Moonnoh R.} and Taehyun Kim and Sandy Johng and Suzanne Rohrback and Nayoung Kang and Choi, {Doo Sup}",
year = "2011",
month = "3",
day = "4",
doi = "10.1016/j.bbrc.2011.01.104",
language = "English (US)",
volume = "406",
pages = "47--52",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Regulation of ethanol-sensitive EAAT2 expression through adenosine A1 receptor in astrocytes

AU - Wu, Jinhua

AU - Lee, Moonnoh R.

AU - Kim, Taehyun

AU - Johng, Sandy

AU - Rohrback, Suzanne

AU - Kang, Nayoung

AU - Choi, Doo Sup

PY - 2011/3/4

Y1 - 2011/3/4

N2 - 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.

AB - 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.

KW - Adenosine A1 receptor

KW - Adenylate cyclase

KW - Alcoholisms

KW - Astrocytes

KW - EAAT2

KW - Glutamate

UR - http://www.scopus.com/inward/record.url?scp=79952189381&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952189381&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2011.01.104

DO - 10.1016/j.bbrc.2011.01.104

M3 - Article

C2 - 21291865

AN - SCOPUS:79952189381

VL - 406

SP - 47

EP - 52

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 1

ER -