title: Phorbol ester-stimulated adherence of neutrophils to endothelial cells is reduced by adenosine A2 receptor agonists.
abstract: In this study we investigated the effect of adenosine receptor agonists on the adherence of PMA-stimulated human neutrophils to cultured porcine aortic endothelial cells. Additionally, we studied the influence of adenosine analogues on the second messenger cAMP in neutrophils and cultured endothelial cells. In the presence of 10 ng/ml PMA, there was a rapid and stable increase on adherence of neutrophils to the endothelial layer. The adenosine A2 receptor agonists, 2-(p-(2-carboxylethyl)phenethylamino)-5' N-ethylcarboxamido-adenosine (CGS 21680) (0.01 to 1 microM) and 5' N-ethylcarboxamidoadenosine (NECA) (0.01 to 1 microM) decreased the adherence of PMA-stimulated neutrophils maximally by 43% and 34%, respectively. In contrast the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (0.01 to 1 microM) showed a 30% increase in PMA-stimulated adherence of neutrophils to endothelial cells. CGS 21680 (0.01 to 1 microM) and NECA (0.01 to 1 microM) were without detectable effect on the formation of cAMP in neutrophils and endothelial cells; however, in the presence of the phosphodiesterase inhibitor Ro 20-1724 (70 microM), CGS 21680 and NECA maximally increased cAMP level 20-fold and 10-fold, respectively, in neutrophils, and 1.8-fold and 2-fold, respectively, in cultured endothelial cells. However, addition of 70 microM Ro 20-1724 to the adherence assay did not potentiate the inhibitory effects of CGS 21680 and NECA on PMA-stimulated neutrophil adherence. On the other hand, 2-chloro-N6-cyclopentyladenosine (0.01 to 1 microM) did not significantly alter cAMP level in neutrophils and endothelial cells in the presence of 4(3-butoxy-4-methoxyphenyl)methyl)-2-imidazolidinone (Ro 20-1724). Our results indicate that adenosine A2 receptor agonists decrease phorbol ester-stimulated adherence of neutrophils to cultured endothelial cells. This effect is possibly independent of adenosine A2 receptor-mediated stimulation of adenylate cyclase in neutrophils and cultured endothelial cells.
authors.affiliation: Institute for Pharmacology, Heinrich-Heine-Universität at Düsseldorf, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Felsch
authors.forename: K
authors.initials: K
authors.lastname: Stöcker
authors.forename: U
authors.initials: U
authors.lastname: Borchard
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D000470:Alkaloids; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate