Adenosine inhibits the release of arachidonic acid and its metabolites (AAM) in activated human peripheral mononuclear cells
The effects of adenosine (Ado) and subtype-specific activators of adenosine receptors (A1, A2A, A2B and A3) were studied on the release of arachidonic acid (AA) and its metabolites (AAM) from human peripheral mononuclear cells (monocytes).
Materials and method:
Adenosine and the selective agonists and antagonists of adenosine receptors were used. 3H-AA and its metabolites released into the medium were determined by measurement of the total 3H radioactivity released without separating the AAM.
In the cells activated by protein kinase C specific phorbol ester (phorbol 12-myristate 13–acetate) and Ca2+ ionophore (A23187), adenosine and two subtype-specific receptor agonists, CPA(A1) and CGS 21680 (A2A) induced concentration-dependent inhibition of the release of AAM, whereas stimulation of A2B or A3 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 A2A and A1 adenosine receptor antagonists, respectively) = IB-MECA. Adenosine inhibited the release of AAM only at and above the concentration of 100 μM, whereas the inhibitory effect of A1 and A2A receptor specific agonists appeared at a concentration of 10-7 M.
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 A2A and A1 receptors can exert, at least in part, an antiinflammatory action by decreasing proinflammatory AAM production.
Keywords:adenosine arachidonic acid arachidonic acid metabolite monocyte
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