Abstract

Extracellular ATP and ATPγS (1–1000 μM) stimulated cyclic AMP (cAMP) production in undifferentiated HL-60 cells. The potency order for adenine nucleotides and adenosine was ATPγS > ATP ⪢ ADP >3AMP = Adenosine. Indomethacin (50 μM) had no effect on ATP-induced cAMP production. ATP and ATPγS also suppressed cell growth and induced differentiation as revealed by fMLP-stimulated β-glucuronidase release 48 h after exposure. The potency order for the induction of fMLP-stimulated β-glucuronidase release by adenine nucleotides and adenosine was ATPγS >3ATP > ADP > AMP = Adenosine ≈ 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 P2Ureceptors 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.

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