PT - JOURNAL ARTICLE AU - Kathleen A. Martin AU - Sylvia B. Kertesy AU - George R. Dubyak TI - Down-Regulation of P<sub>2U</sub>-Purinergic Nucleotide Receptor Messenger RNA Expression During <em>In Vitro</em> Differentiation of Human Myeloid Leukocytes by Phorbol Esters or Inflammatory Activators AID - 10.1124/mol.51.1.97 DP - 1997 Jan 01 TA - Molecular Pharmacology PG - 97--108 VI - 51 IP - 1 4099 - http://molpharm.aspetjournals.org/content/51/1/97.short 4100 - http://molpharm.aspetjournals.org/content/51/1/97.full SO - Mol Pharmacol1997 Jan 01; 51 AB - HL-60 human promyelocytic leukocytes express G protein-coupled P2U-purinergic nucleotide receptors (P2UR or P2Y2R) that activate inositol phospholipid hydrolysis and Ca2+ mobilization in response to ATP or UTP. We examined the expression of functional P2UR and P2UR mRNA levels during in vitro differentiation of HL-60 cells by dibutyryl-cAMP (Bt2cAMP), which induces a granulocyte/neutrophil phenotype, or by phorbol-12-myristate-13-acetate (PMA), which induces a monocyte/macrophage phenotype. Both P2UR function and P2UR mRNA levels were only modestly attenuated during granulocytic differentiation by Bt2cAMP. In contrast, P2UR function, as assayed by either Ca2+ mobilization or inositol trisphosphate generation, was greatly reduced in PMA-differentiated cells. This inhibition of P2UR function was strongly correlated with PMA-induced decreases in P2UR mRNA levels, as assayed by Northern blot analysis or reverse transcription-polymerase chain reaction-based quantification. Although PMA induced an early, transient up-regulation of P2UR mRNA, this was rapidly followed by a sustained decrease in P2UR mRNA to a level 5–10-fold lower than that in undifferentiated HL-60 cells. The half-life of the P2UR transcript in HL-60 cells was ∼60 min, and this was not affected by acute exposure (≤4 hr) to Bt2cAMP or PMA. PMA down-regulated P2UR mRNA in THP-1 monocytes and HL-60 granulocytes but not in A431 human epithelial cells or human keratinocytes. P2UR mRNA was also down-regulated in THP-1 monocytes differentiated into inflammatory macrophages by γ-interferon and endotoxin. These data indicate that myeloid leukocytes possess tissue-specific mechanisms for the rapid modulation of P2UR expression and function during differentiation and inflammatory activation.