Histamine-induced differentiation of HL-60 cells. The role of cAMP and protein kinase A.
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.
Nonaka
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T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Mio
M
M
Doi
M
M
Tasaka
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K
D002227:Carbazoles; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D009504:Neutrophils; D009195:Peroxidase / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology; D011970:Receptors, Histamine H2 / Q000187:drug effects
D002227:Carbazoles; D007211:Indoles; D011758:Pyrroles; D011970:Receptors, Histamine H2; C057416:KT 5720; D002927:Cimetidine; D006632:Histamine; D000242:Cyclic AMP; D009195:Peroxidase; D011494:Protein Kinases