PMID- 11138734 OWN - NLM STAT- MEDLINE DCOM- 20010301 LR - 20190725 IS - 0021-5198 (Print) IS - 0021-5198 (Linking) VI - 84 IP - 3 DP - 2000 Nov TI - Correlation between adenine nucleotide-induced cyclic AMP elevation and extracellular adenosine formation in NG108-15 cells. PG - 325-33 AB - We previously demonstrated that extracellular adenine nucleotides induced cyclic AMP elevation in NG108-15 cells. This response was resistant to adenosine deaminase (ADA) and the ecto-5'-nucleotidase (CD73) inhibitor alpha,beta-methylene ADP (alpha,beta-MeADP), but was inhibited by both P1- and P2-receptor antagonists. In the present study, we investigated the relationship between adenine nucleotide-induced cyclic AMP elevation and extracellular adenosine formation. ATP, AMP and beta,gamma-methylene ATP (beta,gamma-MeATP) were time-dependently metabolized to adenosine in NG108-15 cells. Adenosine formations from ATP, AMP and beta,gamma-MeATP were not affected by alpha,beta-MeADP, but suppressed by the P2-receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS). A close correlation between extracellular adenosine formation and cyclic AMP increasing effects were obtained with several adenine nucleotide agonists in NG108-15 cells as well as their parent cell line C6Bu-1 and N18TG-2 cells, all of which possess functional adenosine A2 receptors. When NG108-15 cells were incubated with [3H]ATP or [3H]AMP in the presence of ADA, [3H]adenosine was found to distribute dominantly on the cell surface. NG108-15 cells expressed mRNA for the ecto-ATPase and nucleotide pyrophosphatase, but not for CD73. These results suggest that local adenosine formation by an ecto-enzyme distinct from CD73 is involved in adenine nucleotide-induced cyclic AMP formation in NG108-15 cells. FAU - Ohkubo, S AU - Ohkubo S AD - Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. FAU - Kimura, J AU - Kimura J FAU - Matsuoka, I AU - Matsuoka I LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Japan TA - Jpn J Pharmacol JT - Japanese journal of pharmacology JID - 2983305R RN - 0 (Adenine Nucleotides) RN - 0 (Enzyme Inhibitors) RN - 0 (Purinergic P2 Receptor Antagonists) RN - 0 (RNA, Messenger) RN - 0T2A5439OE (alpha,beta-methyleneadenosine 5'-diphosphate) RN - 149017-66-3 (pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid) RN - 415SHH325A (Adenosine Monophosphate) RN - 5V5IOJ8338 (Pyridoxal Phosphate) RN - 61D2G4IYVH (Adenosine Diphosphate) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - E0399OZS9N (Cyclic AMP) RN - EC 3.1.3.- (Nucleotidases) RN - EC 3.1.3.31 (nucleotidase) RN - K72T3FS567 (Adenosine) SB - IM MH - Adenine Nucleotides/*metabolism MH - Adenosine/*biosynthesis MH - Adenosine Diphosphate/*analogs & derivatives/pharmacology MH - Adenosine Monophosphate/metabolism/pharmacology MH - Adenosine Triphosphate/metabolism MH - Animals MH - Cell Membrane/metabolism MH - Chromatography, High Pressure Liquid MH - Cyclic AMP/*metabolism MH - Enzyme Inhibitors/pharmacology MH - Extracellular Space/metabolism MH - Nucleotidases/antagonists & inhibitors/metabolism MH - Purinergic P2 Receptor Antagonists MH - Pyridoxal Phosphate/*analogs & derivatives/pharmacology MH - RNA, Messenger/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Cells, Cultured EDAT- 2001/01/04 11:00 MHDA- 2001/03/07 10:01 CRDT- 2001/01/04 11:00 PHST- 2001/01/04 11:00 [pubmed] PHST- 2001/03/07 10:01 [medline] PHST- 2001/01/04 11:00 [entrez] AID - 10.1254/jjp.84.325 [doi] PST - ppublish SO - Jpn J Pharmacol. 2000 Nov;84(3):325-33. doi: 10.1254/jjp.84.325.