Abstract

Human neutrophils have been demonstrated to posses both adenosine A 1 and A 2 receptors: activation of adenosine A 2 receptors inhibits the respiratory burst, assayed as superoxide anion production (O 2 −) from cells stimulated by the bacterial peptide N-formylmethionyl-leucyl-phenylalanine (FMLP). Exposure of neutrophils to different combinations of stimuli results in synergistic or primed responses. These responses can be measured by challenging the cells either with a combination of FMLP and platelet activating factor (PAF), or with a combination of PAF and the neuropeptide substance P, which by itself does not induce O 2 − production. In order to evaluate the ability of adenosine receptor agonists to inhibit O 2 − production by primed or synergistically stimulated neutrophils, a non-selective adenosine receptor agonist, 2-chloroadenosine, was tested in comparison with reportedly selective ligands of adenosine A 1 and A 2 receptor types, N 6-cyclopentyladenosine (CPA) and 2-[4-(2-carboxyethyl) phenethylamino]-5′-N-ethyl-carboxamido adenosine (CGS 21680). The order of activity CGS 21680 > 2-chloroadnosine > CPA indicates that adenosine A 2 receptors mediate the inhibition of the respiratory burst even when neutrophils are primed or synergistically activated. 8-Phenyltheophylline antagonized the effects of these adenosine receptor agonists in a competitive way.

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