EXTRACELLULAR ATP TRIGGERS CYCLIC-AMP-DEPENDENT DIFFERENTIATION OF HL-60 CELLS (VOL 232, PG 626, 1997)

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 much greater than AMP = Adenosine. Indomethacin (50 mu M) h ad 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 potenc y order for the induction of fMLP-stimulated beta-glucuronidase releas e by adenine nucleotides and adenosine was ATP gamma S greater than or equal to ATP > ADP > AMP = Adenosine approximate to 0. The protein ki nase A inhibitor Rp-8-Br-cAMPS (10-200 mu M) suppressed ATP-induced di fferentiation but had no effect on ATP-dependent growth suppression. U TP which, like ATP, activates P-2U receptors on HL-60 cells, had no ef fect on cAMP production, cell growth, or differentiation. The data sug gest the existence of a novel receptor for ATP on undifferentiated HL- 60 cells that is coupled to the activation of adenylate cyclase and cA MP-dependent differentiation. (C) 1997 Academic Press.