title: Extracellular ATP triggers cyclic AMP-dependent differentiation of HL-60 cells.
abstract: Extracellular ATP and ATPgammaS (1-1000 microM) stimulated cyclic AMP (cAMP) production in undifferentiated HL-60 cells. The potency order for adenine nucleotides and adenosine was ATPgammaS > ATP >> ADP > or = AMP = Adenosine. Indomethacin (50 microM) had no effect on ATP-induced cAMP production. ATP and ATPgammaS also suppressed cell growth and induced differentiation as revealed by fMLP-stimulated beta-glucuronidase release 48 h after exposure. The potency order for the induction of fMLP-stimulated beta-glucuronidase release by adenine nucleotides and adenosine was ATPgammaS > or = ATP > ADP > AMP = Adenosine approximately 0. The protein kinase A inhibitor Rp-8-Br-cAMPS (10-200 microM) suppressed ATP-induced differentiation but had no effect on ATP-dependent growth suppression. UTP which, like ATP, activates P2U receptors on HL-60 cells, had no effect on cAMP production, cell growth, or differentiation. The data suggest the existence of a novel receptor for ATP on undifferentiated HL-60 cells that is coupled to the activation of adenylate cyclase and cAMP-dependent differentiation.
authors.affiliation: Department of Biochemistry, University of Sydney, New South Wales, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Jiang
authors.forename: F M
authors.initials: FM
authors.lastname: Foster
authors.forename: P
authors.initials: P
authors.lastname: Ward
authors.forename: V
authors.initials: V
authors.lastname: Tasevski
authors.forename: B M
authors.initials: BM
authors.lastname: Luttrell
authors.forename: A D
authors.initials: AD
authors.lastname: Conigrave
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism*; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans
chemical_list: D000255:Adenosine Triphosphate; D000242:Cyclic AMP