Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-Methyl-3-isobutylxanthine / pharmacology
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Adenine Nucleotides / metabolism
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Adenosine Diphosphate / analogs & derivatives*
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Adenosine Diphosphate / pharmacology
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Adenosine Triphosphate / chemistry
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Adenosine Triphosphate / metabolism*
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Adenosine Triphosphate / pharmacology*
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Antigens, CD / metabolism
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Blotting, Northern
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Cell Differentiation*
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Cell Size / drug effects
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Cyclic AMP / metabolism*
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Dose-Response Relationship, Drug
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Enzyme Activation
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Granulocytes / cytology*
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Granulocytes / drug effects
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Granulocytes / metabolism
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HL-60 Cells
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Humans
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Leukemia, Promyelocytic, Acute
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N-Formylmethionine Leucyl-Phenylalanine / metabolism
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Phosphodiesterase Inhibitors / pharmacology
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Receptors, Formyl Peptide
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism
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Receptors, Peptide / genetics
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Receptors, Peptide / metabolism
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Receptors, Purinergic P2 / genetics
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Receptors, Purinergic P2 / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Thionucleotides / pharmacology
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Tretinoin / pharmacology*
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Tumor Cells, Cultured
Substances
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Adenine Nucleotides
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Antigens, CD
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P2RY11 protein, human
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Phosphodiesterase Inhibitors
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Receptors, Formyl Peptide
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Receptors, Immunologic
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Receptors, Peptide
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Receptors, Purinergic P2
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Thionucleotides
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adenosine 5'-O-(2-thiodiphosphate)
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adenosine 5'-O-(1-thiodiphosphate)
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Tretinoin
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N-Formylmethionine Leucyl-Phenylalanine
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Adenosine Diphosphate
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Adenosine Triphosphate
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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1-Methyl-3-isobutylxanthine