Orphanin FQ/nociceptin and naloxone benzoylhydrazone activate distinct receptors in BE(2)-C human neuroblastoma cells

• Published in: Neuroscience letters Vol. 299; no. 3; pp. 173 - 176
• Main Authors: Mathis, John P, Mandyam, Chitra D, Altememi, Ghazi F, Pasternak, Gavril W, Standifer, Kelly M
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 23.02.2001; Elsevier
• Subjects: Antisense Elements (Genetics) - pharmacology; Binding Sites - drug effects; Binding Sites - physiology; Binding, Competitive - drug effects; Binding, Competitive - physiology; Biological and medical sciences; cAMP; Cell Membrane - drug effects; Cell Membrane - metabolism; Cyclic AMP - metabolism; Homologous desensitization; Humans; Kappa 3 opioid receptor; Medical sciences; Naloxone - analogs & derivatives; Naloxone - pharmacology; Neuroblastoma; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Nociceptin; Nociceptin Receptor; Opioid Peptides - metabolism; Opioid Peptides - pharmacology; Orphan opioid receptor-like receptor; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Radioligand Assay; Receptors, Opioid - chemistry; Receptors, Opioid - drug effects; Receptors, Opioid - metabolism; Receptors, Opioid, kappa - chemistry; Receptors, Opioid, kappa - drug effects; Receptors, Opioid, kappa - metabolism; Subcellular Fractions - drug effects; Subcellular Fractions - metabolism; Tumor Cells, Cultured - drug effects; Tumor Cells, Cultured - metabolism; Orphan opioid receptor-like receptor; cAMP; Kappa 3 opioid receptor; Homologous desensitization; Human; κ Opioid receptor; Cell line; Naloxone; Neuroblastoma; Opioid peptide
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(01)01524-5

κ 3 opioid receptors have a unique binding and analgesic profile, as originally defined by naloxone benzoylhydrazone (NalBzoH). Although antisense studies demonstrated the close relationship between κ 3 opioid and Orphan opioid receptor-like receptor (ORL1) and implied they were generated from the same gene, these studies also revealed differences in the sensitivity profiles of NalBzoH and orphanin FQ/nociceptin (OFQ/N), indicating that they were not identical. To help define the relationship between κ 3 and ORL1 receptors, we utilized BE(2)-C human neuroblastoma cells that natively express functional ORL1 and κ 3 opioid receptors. 125I-[Tyr 14]OFQ/N binds to a single population of receptors in BE(2)-C cells. Competition binding and adenylyl cyclase studies clearly illustrated marked selectivity differences between the ORL1 and the κ 3 sites. Furthermore, antisense DNA targeting ORL1 blocked the inhibition of cAMP by OFQ/N, but not by NalBzoH. Thus, the receptor mechanisms mediating the activity of OFQ/N and NalBzoH in BE(2)-C cells are distinct.