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 (A₁, A_2A, A_2B 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.

Results:

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 (A_2A) induced concentration-dependent inhibition of the release of AAM, whereas stimulation of A_2B 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 A_2A 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 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 A₁ receptors can exert, at least in part, an antiinflammatory action by decreasing proinflammatory AAM production.