PMID- 11158259
OWN - NLM
STAT- MEDLINE
DCOM- 20010315
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 76
IP  - 3
DP  - 2001 Feb
TI  - Beta,gamma-methylene ATP-induced cAMP formation in C6Bu-1 cells: involvement of 
      local metabolism and subsequent stimulation of adenosine A2B receptor.
PG  - 872-80
AB  - The mechanism underlying beta,gamma-methylene ATP (beta,gamma-MeATP)-induced cAMP 
      elevation was investigated in rat glioma C6Bu-1 cells. Beta,gamma-MeATP increased 
      forskolin-stimulated cAMP formation in a manner sensitive to both the P1 
      antagonist xanthine amine congener (XAC) and the P2 antagonist 
      pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS). Adenosine deaminase 
      (ADA; 1 U/mL), which abolished the adenosine-induced response, did not eliminate 
      the beta,gamma-MeATP-induced response. However, combination of ADA with 
      alpha,beta-methylene ADP (alpha,beta-MeADP), an ecto-5'-nucleotidase inhibitor, 
      blocked the beta,gamma-MeATP-induced response. AMP, the substrate for 
      ecto-5'-nucleotidase, also induced cAMP formation in a manner sensitive to XAC 
      and alpha,beta-MeADP inhibition. However, the AMP-induced response was not 
      blocked by PPADS. HPLC analyses revealed that adenosine was generated from 
      beta,gamma-MeATP and AMP. In addition, alpha,beta-MeADP inhibited the conversion 
      of beta,gamma-MeATP and AMP to adenosine, whereas PPADS blocked adenosine 
      formation from beta,gamma-MeATP but not from AMP. [3H]Adenosine generated from 
      [3H]AMP was preserved on the cell surface environment even in the presence of 
      ADA. The mRNAs for ecto-phosphodiesterase/pyrophosphatase 1 (EC 3.1.4.1), 
      ecto-5'-nucleotidase (EC 3.1.3.5) and adenosine A2B receptor were detected by 
      RT-PCR. These results suggest that C6Bu-1 cells possess ecto-enzymes converting 
      beta,gamma-MeATP to adenosine, and the locally accumulated adenosine in this 
      mechanism efficiently stimulates A2B receptors in a manner resistant to exogenous 
      ADA.
FAU - Ohkubo, S
AU  - Ohkubo S
AD  - Department of Pharmacology, School of Medicine, Fukushima Medical University, 
      Fukushima, Japan.
FAU - Kumazawa, K
AU  - Kumazawa K
FAU - Sagawa, K
AU  - Sagawa K
FAU - Kimura, J
AU  - Kimura J
FAU - Matsuoka, I
AU  - Matsuoka I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Purinergic Antagonists)
RN  - 0 (Purinergic P2 Receptor Agonists)
RN  - 0 (Receptor, Adenosine A2B)
RN  - 0 (Receptors, Purinergic P1)
RN  - 1F7A44V6OU (Colforsin)
RN  - 3469-78-1 (5'-adenylyl (beta,gamma-methylene)diphosphonate)
RN  - 415SHH325A (Adenosine Monophosphate)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 3.1.3.- (Nucleotidases)
RN  - EC 3.1.3.5 (5'-Nucleotidase)
RN  - K72T3FS567 (Adenosine)
RN  - NYX13NT29D (alpha,beta-methyleneadenosine 5'-triphosphate)
SB  - IM
MH  - 5'-Nucleotidase/antagonists & inhibitors
MH  - Adenosine/biosynthesis
MH  - Adenosine Monophosphate/metabolism/pharmacology
MH  - Adenosine Triphosphate/*analogs & derivatives/metabolism/*pharmacology
MH  - Animals
MH  - Cell Membrane/metabolism
MH  - Colforsin/pharmacology
MH  - Cyclic AMP/*biosynthesis
MH  - Enzyme Inhibitors/pharmacology
MH  - Extracellular Space/metabolism
MH  - Nucleotidases/metabolism
MH  - Purinergic Antagonists
MH  - Purinergic P2 Receptor Agonists
MH  - Rats
MH  - Receptor, Adenosine A2B
MH  - Receptors, Purinergic P1/*metabolism
MH  - Tumor Cells, Cultured
EDAT- 2001/02/07 11:00
MHDA- 2001/03/17 10:01
CRDT- 2001/02/07 11:00
PHST- 2001/02/07 11:00 [pubmed]
PHST- 2001/03/17 10:01 [medline]
PHST- 2001/02/07 11:00 [entrez]
AID - 10.1046/j.1471-4159.2001.00098.x [doi]
PST - ppublish
SO  - J Neurochem. 2001 Feb;76(3):872-80. doi: 10.1046/j.1471-4159.2001.00098.x.