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

Extracellular ATP and ATP gamma S (1-1000 mu M) stimulated cyclic AMP (cAMP) production in undifferentiated HL-60 cells, The potency order for adenine nucleotides and adenosine was ATP gamma S > ATP much greater than ADP >(3) AMP = Adenosine. Indomethacin (50 mu M) 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 approximate to 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, libe ATP, activates P-2U 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. (C) 1997 Academic Press.