Histamine-induced differentiation of HL-60 cells. The role of cAMP and protein kinase A

Biochem Pharmacol. 1992 Sep 25;44(6):1115-21. doi: 10.1016/0006-2952(92)90375-s.


When HL-60 cells were stimulated with histamine, a significant differentiation of the cells toward neutrophils was elicited. Histamine increased phagocytic activity, but it reduced myeloperoxidase activity of HL-60 cells. Histamine-induced differentiation in HL-60 cells was inhibited not only by H2 antagonists, such as cimetidine, ranitidine and famotidine, but also by an inhibitor of protein kinase A (A kinase), KT-5720. Histamine increased the cAMP level and A kinase activity in HL-60 cells; both increases preceded the cell differentiation. Histamine also enhanced phosphorylation of a 160 kD protein in HL-60 cells, while H2 antagonists and KT-5720 inhibited this phosphorylation. The results of the present study indicate that an activation of A kinase via H2 receptor stimulation may cause the phosphorylation of a 160 kD protein and that this phosphorylation is probably involved in the process leading to differentiation of HL-60 cells.

MeSH terms

  • Carbazoles*
  • Cell Differentiation / drug effects*
  • Cell Line / drug effects
  • Cimetidine / pharmacology
  • Cyclic AMP / metabolism*
  • Enzyme Activation / drug effects
  • Histamine / pharmacology*
  • Humans
  • Indoles / pharmacology
  • Neutrophils
  • Peroxidase / metabolism
  • Phagocytosis / drug effects
  • Phosphorylation / drug effects
  • Protein Kinases / metabolism*
  • Pyrroles / pharmacology
  • Receptors, Histamine H2 / drug effects


  • Carbazoles
  • Indoles
  • Pyrroles
  • Receptors, Histamine H2
  • KT 5720
  • Cimetidine
  • Histamine
  • Cyclic AMP
  • Peroxidase
  • Protein Kinases