title: Diadenosine diphosphate (Ap₂A) delays neutrophil apoptosis via the adenosine A2A receptor and cAMP/PKA pathway.
abstract: Diadenosine polyphosphates have been shown to inhibit neutrophil apoptosis, but mechanisms of the antiapoptotic effect are not known. Diadenosine diphosphate (Ap2A) is the simplest naturally occurring diadenosine polyphosphate, and its effect on neutrophil apoptosis has not previously been investigated. Here we report that Ap2A delays spontaneous apoptosis of human neutrophils, and the effect is reversed by the adenosine A2A receptor antagonists SCH442416 and ZM241385. Ap2A induced an elevation of intracellular cAMP and the elevation was blocked by the adenosine A2A receptor antagonists. The antiapoptotic effect of Ap2A was abrogated by 2',5'-dideoxyadenosine, an inhibitor of adenylyl cyclase, and Rp-8-Br-cAMPS, an inhibitor of type I cAMP-dependent protein kinase A (PKA). Together, these results demonstrate that Ap2A delays neutrophil apoptosis via the adenosine A2A receptor and cAMP/PKA signaling axis.
authors.affiliation: Hematology Research Center, Novy Zykovsky Pr. 4, Moscow 125167, Russia.
authors.forename: Boris K
authors.initials: BK
authors.lastname: Pliyev
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Dimitrieva
authors.forename: Valery G
authors.initials: VG
authors.lastname: Savchenko
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D016048:Dideoxyadenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
chemical_list: C105593:8-bromoadenosine-3',5'-cyclic monophosphorothioate; D058917:Adenosine A2 Receptor Antagonists; D015226:Dinucleoside Phosphates; D011720:Pyrazoles; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D013873:Thionucleotides; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; C012276:diadenosine pyrophosphate; D015124:8-Bromo Cyclic Adenosine Monophosphate; D016048:Dideoxyadenosine; C021008:2',5'-dideoxyadenosine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C416650:SCH 442416
keywords: Ap2A; adenosine A2A receptor; apoptose; apoptosis; neutrophiles; neutrophils; récepteur de l’adénosine A2A