The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) modulate several biochemical pathways in human leukemic myeloid cells

J Neuroimmunol. 2004 Apr;149(1-2):167-81. doi: 10.1016/j.jneuroim.2003.12.008.

Abstract

The neuropeptides Vasoactive-intestinal peptide (VIP) and Pituitary adenylate-cyclase activating protein (PACAP) increased cAMP levels in three out of five human myeloid leukemic cell lines tested while an increased in calcium intracytoplasmic levels was seen only in one cell line (HEL). This increase was phospholipase C, Pertussis toxin dependent and associated with an increase in c-fos and c-jun protein expression together with the formation of functional AP-1 transcriptional factor complex. Cell exposure to VIP or PACAP resulted in a decrease in HEL cell proliferation associated with a down-regulation of the erythroid marker, Glycophorin A. Both peptides were found to increase intra-cytoplasmic calcium levels in blasts isolated from patients with myeloid leukemia. Thus VIP and PACAP are involved in the physiology and pathophysiology of human myeloid cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Bromodeoxyuridine / metabolism
  • Calcium / metabolism
  • Cell Line, Tumor
  • Cyclic AMP / metabolism
  • Cytarabine / pharmacology
  • Cytosol / metabolism
  • DNA Fragmentation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Electrophoretic Mobility Shift Assay / methods
  • Enzyme Inhibitors / pharmacology
  • Enzyme-Linked Immunosorbent Assay / methods
  • Estrenes / pharmacology
  • Flow Cytometry / methods
  • Glycophorins / metabolism
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Inositol Phosphates / metabolism
  • Intercellular Adhesion Molecule-1 / metabolism
  • Leukemia / pathology
  • Myeloid Cells / drug effects*
  • Myeloid Cells / metabolism
  • Neuropeptides / genetics
  • Neuropeptides / pharmacology*
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Protein Binding
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Pyrrolidinones / pharmacology
  • RNA, Messenger / biosynthesis
  • Receptors, Vasoactive Intestinal Peptide / genetics
  • Receptors, Vasoactive Intestinal Peptide / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Signal Transduction / drug effects*
  • Tetradecanoylphorbol Acetate / analogs & derivatives*
  • Tetradecanoylphorbol Acetate / pharmacokinetics
  • Thrombin / pharmacology
  • Time Factors
  • Transcription Factor AP-1 / metabolism
  • Vasoactive Intestinal Peptide / metabolism
  • Vasoactive Intestinal Peptide / pharmacology*

Substances

  • ADCYAP1 protein, human
  • Enzyme Inhibitors
  • Estrenes
  • Glycophorins
  • Immunosuppressive Agents
  • Inositol Phosphates
  • Neuropeptides
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Proto-Oncogene Proteins
  • Pyrrolidinones
  • RNA, Messenger
  • Receptors, Vasoactive Intestinal Peptide
  • Transcription Factor AP-1
  • Cytarabine
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • Intercellular Adhesion Molecule-1
  • inositol pentaphosphate
  • Vasoactive Intestinal Peptide
  • 4-O-methyl-12-O-tetradecanoylphorbol 13-acetate
  • Adenosine Triphosphate
  • Cyclic AMP
  • Thrombin
  • Bromodeoxyuridine
  • Tetradecanoylphorbol Acetate
  • Calcium