adp-beta-s and Leukemia--Promyelocytic--Acute

Priming of NB4 promyelocytic cells with all-trans retinoic acid, followed by extracellular ATP in the presence of a phosphodiesterase inhibitor, elevated cAMP and activated protein kinase A. The order of potency for cAMP production was ATP (EC50 = 95 +/- 13 micromol/L) > ADP > AMP = adenosine. The order of potency of ATP analogues was 2'- and 3'-O-(4-benzoylbenzoyl)-ATP (EC50 = 54 +/- 15 micromol/L) = adenosine 5'-O-(3-thio) triphosphate (EC50 = 66 +/- 4 micromol/L) > ATP > beta,gamma-methylene ATP (EC50 = 200 +/- 55 micromol/L). Adenosine 5'-O-thiomonophosphate and adenosine 5'-O-(2-thio) diphosphate inhibited ATP-induced cAMP production. Differentiation also occurred as measured by increased expression of CD11b and N-formyl peptide receptor and changes in cell morphology. UTP did not elevate cAMP or induce differentiation, indicating that P2Y2, P2Y4, and P2Y6 receptors were not involved. The P2Y11 receptor, a cAMP-linked receptor on promyelocytic HL-60 cells, was detected in NB4 cells by reverse transcription-polymerase chain reaction and northern blotting. This receptor has the same order of potency with respect to cAMP production as that observed in HL-60 cells.

Topics: 1-Methyl-3-isobutylxanthine; Adenine Nucleotides; Adenosine Diphosphate; Adenosine Triphosphate; Antigens, CD; Blotting, Northern; Cell Differentiation; Cell Size; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Dose-Response Relationship, Drug; Enzyme Activation; Granulocytes; HL-60 Cells; Humans; Leukemia, Promyelocytic, Acute; N-Formylmethionine Leucyl-Phenylalanine; Phosphodiesterase Inhibitors; Receptors, Formyl Peptide; Receptors, Immunologic; Receptors, Peptide; Receptors, Purinergic P2; Reverse Transcriptase Polymerase Chain Reaction; Thionucleotides; Tretinoin; Tumor Cells, Cultured