Extracellular ATP triggers cyclic AMP-dependent differentiation of HL-60 cells

Biochem Biophys Res Commun. 1997 Mar 27;232(3):626-30. doi: 10.1006/bbrc.1997.6345.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / analogs & derivatives
  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Adenine Nucleotides / pharmacology
  • Adenosine / pharmacology
  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology*
  • Cell Differentiation / drug effects*
  • Cell Differentiation / physiology*
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cyclic AMP / biosynthesis*
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Enzyme Inhibitors / pharmacology
  • HL-60 Cells
  • Humans
  • Kinetics
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Receptors, Purinergic P2 / drug effects
  • Receptors, Purinergic P2 / metabolism
  • Thionucleotides / pharmacology
  • Uridine Triphosphate / pharmacology

Substances

  • 8-bromoadenosine-3',5'-cyclic monophosphorothioate
  • Adenine Nucleotides
  • Enzyme Inhibitors
  • Receptors, Purinergic P2
  • Thionucleotides
  • 8-Bromo Cyclic Adenosine Monophosphate
  • adenosine 5'-O-(3-thiotriphosphate)
  • N-Formylmethionine Leucyl-Phenylalanine
  • Adenosine Triphosphate
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Adenosine
  • Uridine Triphosphate