PMID- 29205377
OWN - NLM
STAT- MEDLINE
DCOM- 20190508
LR  - 20190508
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 145
IP  - 3
DP  - 2018 May
TI  - Adenosine A(2A) receptors are required for glutamate mGluR5- and dopamine D1 
      receptor-evoked ERK1/2 phosphorylation in rat hippocampus: involvement of NMDA 
      receptor.
PG  - 217-231
LID - 10.1111/jnc.14268 [doi]
AB  - Interaction between mGluR5 and NMDA receptors (NMDAR) is vital for synaptic 
      plasticity and cognition. We recently demonstrated that stimulation of mGluR5 
      enhances NMDAR responses in hippocampus by phosphorylating NR2B(Tyr1472) subunit, 
      and this reaction was enabled by adenosine A(2A) receptors (A(2A) R) (J 
      Neurochem, 135, 2015, 714). In this study, by using in vitro phosphorylation and 
      western blot analysis in hippocampal slices of male Wistar rats, we show that 
      mGluR5 stimulation or mGluR5/NMDARs co-stimulation synergistically activate 
      ERK1/2 signaling leading to c-Fos expression. Interestingly, both reactions are 
      under the permissive control of endogenous adenosine acting through A(2A) Rs. 
      Moreover, mGluR5-mediated ERK1/2 phosphorylation depends on NMDAR, which however 
      exhibits a metabotropic way of function, since no ion influx through its ion 
      channel is required. Furthermore, our results demonstrate that mGluR5 and 
      mGluR5/NMDAR-evoked ERK1/2 activation correlates well with the 
      mGluR5/NMDAR-evoked NR2B(Tyr1472) phosphorylation, since both phenomena coincide 
      temporally, are Src dependent, and are both enabled by A(2A) Rs. This indicates a 
      functional involvement of NR2B(Tyr1472) phosphorylation in the ERK1/2 activation. 
      Our biochemical results are supported by electrophysiological data showing that 
      in CA1 region of hippocampus, the theta burst stimulation (TBS)-induced long-term 
      potentiation coincides temporally with an increase in ERK1/2 activation and both 
      phenomena are dependent on the tripartite A(2A) , mGlu5, and NMDARs. Furthermore, 
      we show that the dopamine D1 receptors evoked ERK1/2 activation as well as the 
      NR2B(Tyr1472) phosphorylation are also regulated by endogenous adenosine and 
      A(2A) Rs. In conclusion, our results highlight the A(2A) Rs as a crucial 
      regulator not only for NMDAR responses, but also for regulating ERK1/2 signaling 
      and its downstream pathways, leading to gene expression, synaptic plasticity, and 
      memory consolidation.
CI  - (c) 2017 International Society for Neurochemistry.
FAU - Krania, Paraskevi
AU  - Krania P
AD  - Physiology Department, Medical School, University of Patras, Patras, Greece.
FAU - Dimou, Eleni
AU  - Dimou E
AD  - Physiology Department, Medical School, University of Patras, Patras, Greece.
FAU - Bantouna, Maria
AU  - Bantouna M
AD  - Physiology Department, Medical School, University of Patras, Patras, Greece.
FAU - Kouvaros, Stylianos
AU  - Kouvaros S
AD  - Physiology Department, Medical School, University of Patras, Patras, Greece.
FAU - Tsiamaki, Eirini
AU  - Tsiamaki E
AD  - Physiology Department, Medical School, University of Patras, Patras, Greece.
FAU - Papatheodoropoulos, Costas
AU  - Papatheodoropoulos C
AD  - Physiology Department, Medical School, University of Patras, Patras, Greece.
FAU - Sarantis, Konstantinos
AU  - Sarantis K
AD  - Physiology Department, Medical School, University of Patras, Patras, Greece.
FAU - Angelatou, Fevronia
AU  - Angelatou F
AUID- ORCID: 0000-0003-0686-0557
AD  - Physiology Department, Medical School, University of Patras, Patras, Greece.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180123
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Grm5 protein, rat)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Receptor, Adenosine A2A)
RN  - 0 (Receptor, Metabotropic Glutamate 5)
RN  - 0 (Receptors, Dopamine D1)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
MH  - Animals
MH  - Gene Expression Regulation/physiology
MH  - Glutamic Acid/metabolism
MH  - Hippocampus/*metabolism
MH  - Long-Term Potentiation/physiology
MH  - MAP Kinase Signaling System/*physiology
MH  - Male
MH  - Memory Consolidation/physiology
MH  - Organ Culture Techniques
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Adenosine A2A/*metabolism
MH  - Receptor, Metabotropic Glutamate 5/*metabolism
MH  - Receptors, Dopamine D1/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
OTO - NOTNLM
OT  - LTP
OT  - A2A receptors
OT  - D1 receptors
OT  - ERK1/2 phosphorylation
OT  - hippocampus
OT  - mGlu5/NMDA receptors
EDAT- 2017/12/06 06:00
MHDA- 2019/05/09 06:00
CRDT- 2017/12/06 06:00
PHST- 2017/07/19 00:00 [received]
PHST- 2017/10/11 00:00 [revised]
PHST- 2017/11/20 00:00 [revised]
PHST- 2017/11/24 00:00 [accepted]
PHST- 2017/12/06 06:00 [pubmed]
PHST- 2019/05/09 06:00 [medline]
PHST- 2017/12/06 06:00 [entrez]
AID - 10.1111/jnc.14268 [doi]
PST - ppublish
SO  - J Neurochem. 2018 May;145(3):217-231. doi: 10.1111/jnc.14268. Epub 2018 Jan 23.