title: Nociceptin-induced internalization of the ORL1 receptor in human neuroblastoma cells.
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.
authors.affiliation: Department of Pharmacology, University of Bologna, Irnerio 48, 40126 Bologna, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Spampinato
authors.forename: R
authors.initials: R
authors.lastname: Di Toro
authors.forename: A R
authors.initials: AR
authors.lastname: Qasem
mesh_terms: D000255:Adenosine Triphosphate / Q000172:deficiency; D019390:Arrestins / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002490:Central Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002966:Clathrin / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018847:Opioid Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000493:pharmacokinetics; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology*; D011869:Radioligand Assay; D011957:Receptors, Opioid / Q000819:agonists* / Q000378:metabolism; D013696:Temperature; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D000255:Adenosine Triphosphate; D019390:Arrestins; D002966:Clathrin; D004791:Enzyme Inhibitors; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000605254:ARRB2 protein, human; C000722283:OPRL1 protein, human