Adenosine modulation of primed human neutrophils.
Human neutrophils have been demonstrated to possess both adenosine A1 and A2 receptors: activation of adenosine A2 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 A1 and A2 receptor types, N6-cyclopentyladenosine (CPA) and 2-[4-(2-carboxyethyl)phenethylamino]-5'-N-ethyl-carboxamido adenosine (CGS 21680). The order of activity CGS 21680 > 2-chloroadenosine > CPA indicates that adenosine A2 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.
Dianzani
C
C
Institute of Pharmacology and Pharmacognosy, University of Turin, Italy.
Brunelleschi
S
S
Viano
I
I
Fantozzi
R
R
D015762:2-Chloroadenosine / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D000959:Antihypertensive Agents; D010627:Phenethylamines; D018047:Receptors, Purinergic P1; D013481:Superoxides; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D015762:2-Chloroadenosine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine