孤啡肽/痛敏肽和纳洛酮苯甲酰腙在BE(2)-C人神经母细胞瘤细胞中激活不同的受体。

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

作者信息

Mathis J P, Mandyam C D, Altememi G F, Pasternak G W, Standifer K M

机构信息

The Cotzias Laboratory of Neuro-Oncology, Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

出版信息

Neurosci Lett. 2001 Feb 23;299(3):173-6. doi: 10.1016/s0304-3940(01)01524-5.

DOI:10.1016/s0304-3940(01)01524-5

PMID:11165763

Abstract

kappa(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 kappa(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 kappa(3) and ORL1 receptors, we utilized BE(2)-C human neuroblastoma cells that natively express functional ORL1 and kappa(3) opioid receptors. (125)I-[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 kappa(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.

摘要

κ(3)阿片受体具有独特的结合和镇痛特性，最初由纳洛酮苯甲酰腙（NalBzoH）定义。尽管反义研究表明κ(3)阿片受体与孤儿阿片样受体（ORL1）之间存在密切关系，并暗示它们来自同一基因，但这些研究也揭示了NalBzoH和孤啡肽/痛敏肽（OFQ/N）在敏感性方面存在差异，表明它们并不相同。为了帮助确定κ(3)和ORL1受体之间的关系，我们利用了天然表达功能性ORL1和κ(3)阿片受体的BE(2)-C人神经母细胞瘤细胞。(125)I-[酪氨酸(14)]OFQ/N与BE(2)-C细胞中的单一受体群体结合。竞争结合和腺苷酸环化酶研究清楚地表明了ORL1和κ(3)位点之间存在明显的选择性差异。此外，靶向ORL1的反义DNA阻断了OFQ/N对cAMP的抑制作用，但未阻断NalBzoH的作用。因此，在BE(2)-C细胞中介导OFQ/N和NalBzoH活性的受体机制是不同的。