Inhibition of ligand binding to G protein-coupled receptors by arachidonic acid Journal Article uri icon
  • Arachidonic acid (AA), released in response to muscarinic acetylcholine receptor (mAChR) stimulation, previously has been reported to function as a reversible feedback inhibitor of the mAChR. To determine if the effects of AA on binding to the mAChR are subtype specific and whether AA inhibits ligand binding to other G protein-coupled receptors (GPCRs), the effects of AA on ligand binding to the mAChR subtypes (M1, M2, M3, M4, and M5) and to the micro-opioid receptor, beta2-adrenergic receptor (beta2-AR), 5-hydroxytryptamine receptor (5-HTR), and nicotinic receptors were examined. AA was found to inhibit ligand binding to all mAChR subtypes, to the beta2-AR, the 5-HTR, and to the micro-opioid receptor. However, AA does not inhibit ligand binding to the nicotinic receptor, even at high concentrations of AA. Thus, AA inhibits several types of GPCRs, with 50% inhibition occurring at 3-25 MuM, whereas the nicotinic receptor, a non-GPCR, remains unaffected. Further research is needed to determine the mechanism by which AA inhibits GPCR function.

  • Link to Article
    publication date
  • 2005
  • published in
  • Adrenergic beta-Antagonists/chemistry/metabolism
  • Animals
  • Arachidonic Acid/chemistry/*metabolism
  • Dihydroalprenolol/chemistry/metabolism
  • Diprenorphine/chemistry/metabolism
  • Ligands
  • Molecular Structure
  • Muscarinic Antagonists/chemistry/metabolism
  • N-Methylscopolamine/chemistry/metabolism
  • Narcotic Antagonists/chemistry/metabolism
  • Parasympatholytics/chemistry/metabolism
  • Protein Binding
  • Protein Isoforms/metabolism
  • Quinuclidinyl Benzilate/chemistry/metabolism
  • Radioligand Assay
  • Receptors, Adrenergic, beta-2/*metabolism
  • Receptors, G-Protein-Coupled/*metabolism
  • Receptors, Muscarinic/*metabolism
  • Receptors, Opioid, mu/*metabolism
  • Receptors, Serotonin/*metabolism
  • Serotonin/chemistry/metabolism
  • Additional Document Info
  • 27
  • issue
  • 2