title: Adenosine inhibits the release of arachidonic acid and its metabolites (AAM) in activated human peripheral mononuclear cells.
abstract: OBJECTIVE
  The effects of adenosine (Ado) and subtype-specific activators of adenosine receptors (A(1), A(2A), A(2B) and A(3)) were studied on the release of arachidonic acid (AA) and its metabolites (AAM) from human peripheral mononuclear cells (monocytes).
  
  
  METHODS
  Adenosine and the selective agonists and antagonists of adenosine receptors were used. (3)H-AA and its metabolites released into the medium were determined by measurement of the total (3)H radioactivity released without separating the AAM.
  
  
  RESULTS
  In the cells activated by protein kinase C specific phorbol ester (phorbol 12-myristate 13-acetate) and Ca(2+) ionophore (A23187), adenosine and two subtype-specific receptor agonists, CPA(A(1)) and CGS 21680 (A(2A)) induced concentration-dependent inhibition of the release of AAM, whereas stimulation of A(2B) or A(3) receptors was ineffective. The rank order of potency for the inhibition of AAM release was as follows: CGS 21680 = CPA > adenosine > NECA (in the presence of ZM 24185 and DPCPX as A(2A) and A(1) adenosine receptor antagonists, respectively) = IB-MECA. Adenosine inhibited the release of AAM only at and above the concentration of 100 muM, whereas the inhibitory effect of A(1) and A(2A) receptor specific agonists appeared at a concentration of 10(-7) M.
  
  
  CONCLUSIONS
  It can be concluded that adenosine physiologically may not have a significant effect on the AAM release of circulating monocytes, but in pathological conditions, where the local Ado concentrations increases, this nucleoside, through activation of A(2A) and A(1) receptors can exert, at least in part, an antiinflammatory action by decreasing proinflammatory AAM production.
authors.affiliation: 3rd Department of Internal Medicine, University of Debrecen, Medical and Health Science Center, Móricz Zs. blv. 22, 4004 Debrecen, Hungary. sipka@iiibel.dote.hu
authors.forename: S
authors.initials: S
authors.lastname: Sipka
authors.forename: I
authors.initials: I
authors.lastname: Kovács
authors.forename: S
authors.initials: S
authors.lastname: Szántó
authors.forename: G
authors.initials: G
authors.lastname: Szegedi
authors.forename: L
authors.initials: L
authors.lastname: Brugós
authors.forename: G
authors.initials: G
authors.lastname: Bruckner
authors.forename: A J
authors.initials: AJ
authors.lastname: Szentmiklósi
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D007476:Ionophores; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D016718:Arachidonic Acid; D000001:Calcimycin; D000242:Cyclic AMP; D011493:Protein Kinase C; D000241:Adenosine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium