Propentofylline enhancement of the actions of adenosine on neutrophil leukocytes.
In agreement with previous results, activation of adenosine A2 receptors was found to inhibit the exocytotic release of elastase and the oxidative burst induced by formyl-MetLeuPhe (fMLP) in human neutrophils. The adenosine analogue 5'-N-ethylcarboxamidoadenosine (NECA) was more potent than adenosine (IC50 14 vs 64 nM). The effects of adenosine and NECA were not influenced by the A1-adenosine receptor selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 300 nM), but were abolished by the non-selective adenosine receptor antagonist 9-chloro-2-(2-furanyl)-5,6-dihydro-[1,2,4]-triazolo[1,5]quinazolin -5-imine monomethanesulfonate (CGS 15943; 10 microM). Propentofylline per se caused a concentration-dependent inhibition of H2O2 production. At 100 microM propentofylline significantly enhanced the effect of adenosine, but not that of NECA. This effect of propentofylline was shared by the known uptake inhibitor dipyridamole. Neither adenosine nor propentofylline altered fMLP-induced inositol-(1,4,5)-trisphosphate (IP3) formation. The results demonstrate that propentofylline can counteract neutrophil activation, at least partly by enhancing the action of adenosine through blocking its removal, and that the effect is exerted at a step after the initial receptor events.
Zhang
Y
Y
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Fredholm
B B
BB
D000241:Adenosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D004357:Drug Synergism; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000187:drug effects*; D010196:Pancreatic Elastase / Q000032:analysis; D058915:Purinergic P1 Receptor Antagonists; D016897:Respiratory Burst / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology*
D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; D019830:Adenosine-5'-(N-ethylcarboxamide); D009240:N-Formylmethionine Leucyl-Phenylalanine; C032114:propentofylline; D006861:Hydrogen Peroxide; D010196:Pancreatic Elastase; D000241:Adenosine