PMID- 20374202
OWN - NLM
STAT- MEDLINE
DCOM- 20101028
LR  - 20220309
IS  - 1530-0277 (Electronic)
IS  - 0145-6008 (Print)
IS  - 0145-6008 (Linking)
VI  - 34
IP  - 6
DP  - 2010 Jun
TI  - ENT1 regulates ethanol-sensitive EAAT2 expression and function in astrocytes.
PG  - 1110-7
LID - 10.1111/j.1530-0277.2010.01187.x [doi]
AB  - BACKGROUND: Equilibrative nucleoside transporter 1 (ENT1) and excitatory amino 
      acid transporter 2 (EAAT2) are predominantly expressed in astrocytes where they 
      are thought to regulate synaptic adenosine and glutamate levels. Because mice 
      lacking ENT1 display increased glutamate levels in the ventral striatum, we 
      investigated whether ENT1 regulates the expression and function of EAAT2 in 
      astrocytes, which could contribute to altered glutamate levels in the striatum. 
      METHODS: We examined the effect of ENT1 inhibition and overexpression on the 
      expression of EAAT2 using quantitative real-time PCR and measured glutamate 
      uptake activity in cultured astrocytes. We also examined the effect of 0 to 200 
      mM ethanol doses for 0 to 24 hours of ethanol exposure on EAAT2 expression and 
      glutamate uptake activity. We further examined the effect of ENT1 knockdown by a 
      specific siRNA on ethanol-induced EAAT2 expression. RESULTS: An ENT1-specific 
      antagonist and siRNA treatments significantly reduced both EAAT2 expression and 
      glutamate uptake activity while ENT1 overexpression up-regulated EAAT2 mRNA 
      expression. Interestingly, 100 or 200 mM ethanol exposure increased EAAT2 mRNA 
      expression as well as glutamate uptake activity. Moreover, we found that ENT1 
      knockdown inhibited the ethanol-induced EAAT2 up-regulation. CONCLUSIONS: Our 
      results suggest that ENT1 regulates glutamate uptake activity by altering EAAT2 
      expression and function, which might be implicated in ethanol intoxication and 
      preference.
FAU - Wu, Jinhua
AU  - Wu J
AD  - Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic 
      College of Medicine, Rochester, Minnesota 55905, USA.
FAU - Lee, Moonnoh R
AU  - Lee MR
FAU - Choi, Sun
AU  - Choi S
FAU - Kim, Taehyun
AU  - Kim T
FAU - Choi, Doo-Sup
AU  - Choi DS
LA  - eng
GR  - P20 AA017830/AA/NIAAA NIH HHS/United States
GR  - AA015164/AA/NIAAA NIH HHS/United States
GR  - AA017830-PROJECT 1/AA/NIAAA NIH HHS/United States
GR  - R01 AA018779/AA/NIAAA NIH HHS/United States
GR  - AA018779/AA/NIAAA NIH HHS/United States
GR  - R01 AA015164/AA/NIAAA NIH HHS/United States
GR  - R01 AA015164-05/AA/NIAAA NIH HHS/United States
GR  - R01 AA018779-01/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100405
PL  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Equilibrative Nucleoside Transporter 1)
RN  - 0 (Excitatory Amino Acid Transporter 2)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (SLC29A1 protein, mouse)
RN  - 0 (Slc1a2 protein, mouse)
RN  - 0 (Thionucleotides)
RN  - 3K9958V90M (Ethanol)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 46S541971T (Thioinosine)
RN  - 65199-10-2 (nitrobenzylthioinosine 5'-monophosphate)
SB  - IM
MH  - Animals
MH  - Astrocytes/cytology/*drug effects/*metabolism
MH  - Cell Line
MH  - Central Nervous System Depressants/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Equilibrative Nucleoside Transporter 1/antagonists & inhibitors/*metabolism
MH  - Ethanol/*pharmacology
MH  - Excitatory Amino Acid Transporter 2/*metabolism
MH  - Glutamic Acid/metabolism
MH  - Mice
MH  - RNA, Small Interfering/pharmacology
MH  - Thioinosine/analogs & derivatives/pharmacology
MH  - Thionucleotides/pharmacology
MH  - Time Factors
PMC - PMC2913860
MID - NIHMS221220
EDAT- 2010/04/09 06:00
MHDA- 2010/10/29 06:00
PMCR- 2010/08/02
CRDT- 2010/04/09 06:00
PHST- 2010/04/09 06:00 [entrez]
PHST- 2010/04/09 06:00 [pubmed]
PHST- 2010/10/29 06:00 [medline]
PHST- 2010/08/02 00:00 [pmc-release]
AID - ACER1187 [pii]
AID - 10.1111/j.1530-0277.2010.01187.x [doi]
PST - ppublish
SO  - Alcohol Clin Exp Res. 2010 Jun;34(6):1110-7. doi: 
      10.1111/j.1530-0277.2010.01187.x. Epub 2010 Apr 5.