Extracellular ATP triggers cyclic AMP-dependent differentiation of HL-60 cells.
Extracellular ATP and ATP gamma S (1-1000 microM) stimulated cyclic AMP (cAMP) production in undifferentiated HL-60 cells. The potency order for adenine nucleotides and adenosine was ATP gamma S > ATP > > ADP > 3 AMP = Adenosine. Indomethacin (50 microM) had no effect on ATP-induced cAMP production. ATP and ATP gamma S 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 ATP gamma S > 3 ATP > ADP > AMP = Adenosine approximately 0. The protein kinase A inhibitor Rp-8-Br-cAMPS (10-200 mM) 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.
Jiang
L
L
Department of Biochemistry, University of Sydney, New South Wales, Australia.
Foster
F M
FM
Ward
P
P
Tasevski
V
V
Luttrell
B M
BM
Conigrave
A D
AD
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000227:Adenine Nucleotides / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000096:biosynthesis*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology
C105593:8-bromoadenosine-3',5'-cyclic monophosphorothioate; D000227:Adenine Nucleotides; D004791:Enzyme Inhibitors; D018048:Receptors, Purinergic P2; D013873:Thionucleotides; D015124:8-Bromo Cyclic Adenosine Monophosphate; C022571:adenosine 5'-O-(3-thiotriphosphate); D009240:N-Formylmethionine Leucyl-Phenylalanine; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000241:Adenosine; D014544:Uridine Triphosphate