Biphasic effect of ATP on neutrophil functions mediated by P2U and adenosine A2A receptors.
In agreement with previous findings, the oxidative burst induced by fMet-Leu-Phe (fMLP) in polymorphonuclear neutrophils was enhanced by adenosine triphosphate (ATP) and uridine 5'-triphosphate (UTP), although these nucleotides were inactive as agonists per se. However, the enhancement by ATP was rapidly reversed to an inhibition by prolonged incubation. Adenosine diphosphate (ADP) was always inhibitory. Inhibition mediated by ATP coincided with its conversion into ADP, adenosine monophosphate (AMP), and adenosine. In addition, the inhibitory effects of ATP and ADP on the oxidative burst were virtually abolished by 9-chloro-2-(2-furanyl)-5,6-dihydro-[1,2,4]-triazolo[1,5] quinazolin-5-imine monomethanesulfonate (CGS 15943), a nonselective adenosine receptor antagonist, whereas the priming effect of ATP was antagonized by adenosine. Both ATP and UTP showed a similar potency in activating elastase release, intracellular inositol-(1,4,5)-triphosphate (IP3) formation and an increase in cytosolic calcium. Neither ATP nor UTP affected the initial rise in cytosolic calcium induced by fMLP, but did enhance the secondary calcium increase. When added simultaneously with fMLP, ADP and adenosine abolished this second calcium peak without influencing the first. These results indicate that purine and pyrimidine nucleotides acting on P2U-like receptors, which are coupled to the IP3 pathway, can increase calcium, release elastase, and enhance the oxidative burst induced by chemo-kines. Adenosine formed by hydrolysis from ATP and ADP, by contrast, reduces the oxidative bursts and the influx of extracellular calcium induced by fMLP.
Zhang
Y
Y
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Palmblad
J
J
Fredholm
B B
BB
D000241:Adenosine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D019272:Leukocyte Elastase; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010196:Pancreatic Elastase / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D018048:Receptors, Purinergic P2 / Q000187:drug effects*; D014544:Uridine Triphosphate / Q000494:pharmacology
D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D000244:Adenosine Diphosphate; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D000241:Adenosine; D002118:Calcium; D014544:Uridine Triphosphate