title: Cyclic AMP-independent activation of neutrophil-like HL-60 cells by prostaglandin E2.
abstract: The role of cAMP in mediating prostaglandin E2 (PGE2)-stimulated aggregation of neutrophil-like HL-60 cells has been investigated. Although the EP2 receptors appear to couple to Gs-proteins, PGE2 stimulated HL-60 cell aggregation appears to be a cAMP-independent process. This response to PGE2 in independent of calcium and tyrosine kinase activity, appears to involve activation of phosphatidylinositol 3-kinase which is negatively regulated by phosphatidic acid generated from phospholipase D activity, and is partially dependent on protein kinase C activity. In contrast, although the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) produces a similar aggregation response to PGE2, FMLP uses a distinct intracellular signalling pathway. The aggregation response to FMLP involves activation of Gi-proteins, is partially dependent on extracellular calcium, is negatively regulated by protein kinase C, and is independent of phosphatidylinositol 3-kinase, phospholipase D and tyrosine kinase activity. The possibility exists that EP2 receptor activation leads to Gs-dependent, but cAMP-independent, stimulation of phosphatidylinositol 3-kinase activity in HL-60 cells.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N. T., Hong Kong.
authors.forename: Z
authors.initials: Z
authors.lastname: Xie
authors.forename: H
authors.initials: H
authors.lastname: Wise
mesh_terms: D002449:Cell Aggregation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology*; D018922:HL-60 Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D009504:Neutrophils; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000242:Cyclic AMP; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D010739:Phospholipase D; D015232:Dinoprostone