Extracellular ATP triggers cyclic AMP-dependent differentiation of HL-60 cells.
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.
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
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
D000255:Adenosine Triphosphate; D000242:Cyclic AMP