Desensitization of the delta-opioid receptor correlates with its phosphorylation in SK-N-BE cells: involvement of a G protein-coupled receptor kinase

J Neurochem. 1998 May;70(5):2129-38. doi: 10.1046/j.1471-4159.1998.70052129.x.


Phosphorylation of G protein-coupled receptors is considered an important step during their desensitization. In SK-N-BE cells, recently presented as a pertinent model for the studies of the human delta-opioid receptor, pretreatment with the opioid agonist etorphine increased time-dependently the rate of phosphorylation of a 51-kDa membrane protein. Immunological characterization of this protein with an antibody, raised against the amino-terminal region of the cloned human delta-opioid receptor, revealed that it corresponded to the delta-opioid receptor. During prolonged treatment with etorphine, phosphorylation increased as early as 15 min to reach a maximum within 1 h. Phosphorylation and desensitization of adenylyl cyclase inhibition paralleled closely and okadaic acid inhibited the resensitization, a result strongly suggesting that phosphorylation of the delta-opioid receptor plays a prominent role in its rapid desensitization. The increase in phosphorylation of the delta-opioid receptor, as well as its desensitization, was not affected by H7, an inhibitor of protein kinase A and protein kinase C, but was drastically reduced by heparin or Zn2+, known to act as G protein-coupled receptor kinase (GRK) inhibitors. These results are the first to show, on endogenously expressed human delta-opioid receptor, that a close link exists between receptor phosphorylation and agonist-promoted desensitization and that desensitization involves a GRK.

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Analgesics, Opioid / pharmacology*
  • Enzyme Inhibitors / pharmacology
  • Etorphine / pharmacology*
  • GTP-Binding Proteins / metabolism*
  • Heparin / pharmacology
  • Humans
  • Membrane Proteins / metabolism
  • Molecular Weight
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Kinase Inhibitors
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Receptors, Opioid, delta / drug effects*
  • Receptors, Opioid, delta / metabolism*
  • Tumor Cells, Cultured
  • Zinc / pharmacology


  • Analgesics, Opioid
  • Enzyme Inhibitors
  • Membrane Proteins
  • Phosphoproteins
  • Protein Kinase Inhibitors
  • Receptors, Opioid, delta
  • Etorphine
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Heparin
  • Receptor Protein-Tyrosine Kinases
  • GTP-Binding Proteins
  • Zinc