PMID- 22691937
OWN - NLM
STAT- MEDLINE
DCOM- 20121109
LR  - 20131121
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 522
IP  - 1
DP  - 2012 Jul 26
TI  - Trk and cAMP-dependent survival activity of adenosine A(2A) agonist CGS21680 on 
      rat motoneurons in culture.
PG  - 21-4
LID - 10.1016/j.neulet.2012.06.003 [doi]
AB  - The survival activity of adenosine A(2A) agonist CGS21680 on motoneurons in 
      culture through the transactivation of neurotrophin receptor TrkB has been 
      reported previously; however, since adenosine A(2A) receptor belongs to a 
      Gs-protein-coupled receptor, we investigated the involvement of the cAMP pathway 
      in the survival activity of CGS21680 using purified motoneurons in culture. 
      CGS21680 alone showed only small survival activity, but the activity was 
      significantly enhanced by the addition of a phosphodiesterase inhibitor, IBMX. 
      This survival activity was partially inhibited by a protein kinase A inhibitor 
      H89 or a neurotrophin receptor tyrosine kinase inhibitor K252a, and was 
      completely inhibited by their combination. These results indicate that the 
      survival activity of CGS21680 on motoneurons is exerted by the mixed effect of 
      the adenylate cyclase-cAMP-PKA pathway and transactivation of Trk neurotrophin 
      receptor. Under conditions in which the maximum survival of motoneurons was 
      supported by sufficient concentrations of brain-derived neurotrophic factor 
      (BDNF), a TrkB ligand, the addition of 100muM AMPA for 3 days led to significant 
      cell death. Treatment with CGS21680 and IBMX protected motoneurons from the 
      toxicity of AMPA, further supporting the presence of a TrkB-independent pathway 
      of CGS21680 activity and suggesting a novel therapeutic approach to motoneuron 
      diseases such as amyotrophic lateral sclerosis.
CI  - Copyright (c) 2012 Elsevier Ireland Ltd. All rights reserved.
FAU - Komaki, Satoshi
AU  - Komaki S
AD  - Clinical Research Support Center, The University of Tokyo Hospital, Faculty of 
      Medicine, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-8655, Japan. 
      s.koma0319@gmail.com
FAU - Ishikawa, Kiichiro
AU  - Ishikawa K
FAU - Arakawa, Yoshihiro
AU  - Arakawa Y
LA  - eng
PT  - Journal Article
DEP - 20120609
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Adenosine A2 Receptor Agonists)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Phenethylamines)
RN  - 0 (Receptor, Adenosine A2A)
RN  - 120225-54-9 (2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine)
RN  - 77521-29-0 (alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/*analogs & derivatives/pharmacology
MH  - Adenosine A2 Receptor Agonists/*pharmacology
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cyclic AMP/*physiology
MH  - Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/physiology
MH  - Humans
MH  - Motor Neurons/cytology/*drug effects/metabolism
MH  - Neuroprotective Agents/pharmacology
MH  - Phenethylamines/*pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Adenosine A2A/*metabolism
MH  - Receptor, trkA/antagonists & inhibitors/*physiology
MH  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology
EDAT- 2012/06/14 06:00
MHDA- 2012/11/10 06:00
CRDT- 2012/06/14 06:00
PHST- 2012/04/15 00:00 [received]
PHST- 2012/05/27 00:00 [revised]
PHST- 2012/06/01 00:00 [accepted]
PHST- 2012/06/14 06:00 [entrez]
PHST- 2012/06/14 06:00 [pubmed]
PHST- 2012/11/10 06:00 [medline]
AID - S0304-3940(12)00775-6 [pii]
AID - 10.1016/j.neulet.2012.06.003 [doi]
PST - ppublish
SO  - Neurosci Lett. 2012 Jul 26;522(1):21-4. doi: 10.1016/j.neulet.2012.06.003. Epub 
      2012 Jun 9.