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 f or adenine nucleotides and adenosine was ATP gamma S > ATP much greate r than ADP >(3) AMP = Adenosine. Indomethacin (50 mu M) had no effect on ATP-induced cAMP production, ATP and ATP gamma S also suppressed ce ll growth and induced differentiation as revealed by fMLP-stimulated b eta-glucuronidase release 48 h after exposure, The potency order for t he induction of fMLP-stimulated beta-glucuronidase release by adenine nucleotides and adenosine was ATP gamma S >(3) ATP > ADP > AMP = Adeno sine approximate to 0. The protein kinase A inhibitor Rp-8-Br-cAMPS (1 0-200 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 growt h, or differentiation. The data suggest the existence of a novel recep tor for ATP on undifferentiated HL-60 cells that is coupled to the act ivation of adenylate cyclase and cAMP-dependent differentiation. (C) 1 997 Academic Press.