Nociceptin-induced internalization of the ORL1 receptor in human neuroblastoma cells

Neuroreport. 2001 Oct 8;12(14):3159-63. doi: 10.1097/00001756-200110080-00035.

Abstract

Nociceptin/orphanin FQ (NC) has been proposed as endogenous ligand of the opioid receptor-like 1 (ORL1) receptor. We investigated NC-induced internalization and recycling of the ORL1 receptor in SK-N-BE human neuroblastoma cells. Internalization was proven by receptor binding assay on viable cells. NC promotes a time- and concentration-dependent internalization of the ORL1 receptor (57% of cell surface receptors are lost after 30 min exposure to 1 microM NC) in a clathrin- and ATP- dependent manner. After 30 min exposure to NC, ORL1 receptor internalization is partially reversible and recycling is dependent on acid phosphatases. Over-expression of beta-arrestin 2 increases NC-promoted internalization of the ORL1 receptor. These events contribute to NC signaling in neuronal cells through sequestration and recycling of the ORL1 receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / deficiency
  • Arrestins / genetics
  • Arrestins / metabolism
  • Binding Sites / drug effects
  • Binding Sites / physiology
  • Central Nervous System / cytology
  • Central Nervous System / drug effects
  • Central Nervous System / metabolism*
  • Clathrin / antagonists & inhibitors
  • Clathrin / metabolism
  • Dose-Response Relationship, Drug
  • Endocytosis / drug effects
  • Endocytosis / physiology*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Neuroblastoma
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Opioid Peptides / antagonists & inhibitors
  • Opioid Peptides / metabolism*
  • Opioid Peptides / pharmacokinetics
  • Protein Transport / drug effects
  • Protein Transport / physiology*
  • Radioligand Assay
  • Receptors, Opioid / agonists*
  • Receptors, Opioid / metabolism
  • Temperature
  • Time Factors
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism*
  • beta-Arrestin 2
  • beta-Arrestins

Substances

  • ARRB2 protein, human
  • Arrestins
  • Clathrin
  • Enzyme Inhibitors
  • Opioid Peptides
  • Receptors, Opioid
  • beta-Arrestin 2
  • beta-Arrestins
  • nociceptin
  • Adenosine Triphosphate
  • nociceptin receptor