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

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• 作者：Mathis ; John P. ; Mandyam ; Chitra D. ; Altememi ; Ghazi F. ; Pasternak ; Gavril W. ; Standifer ; Kelly M.
• 关键词：Orphan opioid receptor-like receptor ; cAMP ; Homologous desensitization ; Kappa₃ opioid receptor
• 刊名：Neuroscience Letters
• 出版年：2001
• 出版时间：February 23, 2001
• 年：2001
• 卷：299
• 期：3
• 页码：173-176
• 全文大小：126 K

文摘

κ₃ opioid receptors have a unique binding and analgesic profile, as originally defined by naloxone benzoylhydrazone (NalBzoH). Although antisense studies demonstrated the close relationship between κ₃ 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 κ₃ and ORL1 receptors, we utilized BE(2)-C human neuroblastoma cells that natively express functional ORL1 and κ₃ opioid receptors. ¹²⁵I-[Tyr¹⁴]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 κ₃ 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.