阿片样物质受体样（ORL1）受体在大鼠中枢神经系统中的分布：ORL1受体mRNA表达与[¹²⁵I]-[(¹⁴)Tyr]-孤啡肽FQ结合的比较

Opioid receptor-like (ORL1) receptor distribution in the rat central nervous system: comparison of ORL1 receptor mRNA expression with (125)I-[(14)Tyr]-orphanin FQ binding.

作者信息

Neal C R, Mansour A, Reinscheid R, Nothacker H P, Civelli O, Akil H, Watson S J

机构信息

Mental Health Research Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0720, USA.

出版信息

J Comp Neurol. 1999 Oct 4;412(4):563-605.

PMID:10464356

Abstract

The recently discovered neuropeptide orphanin FQ (OFQ), and its opioid receptor-like (ORL1) receptor, exhibit structural features suggestive of the micro, kappa, and delta opioid systems. The anatomic distribution of OFQ immunoreactivity and mRNA expression has been reported recently. In the present analysis, we compare the distribution of orphanin receptor mRNA expression with that of orphanin FQ binding at the ORL1 receptor in the adult rat central nervous system (CNS). By using in vitro receptor autoradiography with (125)I-[(14)Tyr]-OFQ as the radioligand, orphanin receptor binding was analyzed throughout the rat CNS. Orphanin binding sites were densest in several cortical regions, the anterior olfactory nucleus, lateral septum, ventral forebrain, several hypothalamic nuclei, hippocampal formation, basolateral and medial amygdala, central gray, pontine nuclei, interpeduncular nucleus, substantia nigra, raphe complex, locus coeruleus, vestibular nuclear complex, and the spinal cord. By using in situ hybridization, cells expressing ORL1 mRNA were most numerous throughout multiple cortical regions, the anterior olfactory nucleus, lateral septum, endopiriform nucleus, ventral forebrain, multiple hypothalamic nuclei, nucleus of the lateral olfactory tract, medial amygdala, hippocampal formation, substantia nigra, ventral tegmental area, central gray, raphe complex, locus coeruleus, multiple brainstem motor nuclei, inferior olive, deep cerebellar nuclei, vestibular nuclear complex, nucleus of the solitary tract, reticular formation, dorsal root ganglia, and spinal cord. The diffuse distribution of ORL1 mRNA and binding supports an extensive role for orphanin FQ in a multitude of CNS functions, including motor and balance control, reinforcement and reward, nociception, the stress response, sexual behavior, aggression, and autonomic control of physiologic processes.

摘要

最近发现的神经肽孤啡肽FQ（OFQ）及其阿片样受体（ORL1）受体，呈现出与μ、κ和δ阿片样系统相似的结构特征。最近已有关于OFQ免疫反应性和mRNA表达的解剖分布报道。在本分析中，我们比较了成年大鼠中枢神经系统（CNS）中孤啡肽受体mRNA表达分布与ORL1受体上孤啡肽FQ结合的分布情况。通过使用以（125）I - [（14）Tyr] - OFQ作为放射性配体的体外受体放射自显影技术，对整个大鼠中枢神经系统的孤啡肽受体结合进行了分析。孤啡肽结合位点在几个皮质区域、前嗅核、外侧隔、腹侧前脑、几个下丘脑核、海马结构、基底外侧和内侧杏仁核、中央灰质、脑桥核、脚间核、黑质、中缝复合体、蓝斑、前庭核复合体以及脊髓中最为密集。通过原位杂交技术，表达ORL1 mRNA的细胞在多个皮质区域、前嗅核、外侧隔、内梨状核、腹侧前脑、多个下丘脑核、外侧嗅束核、内侧杏仁核、海马结构、黑质、腹侧被盖区、中央灰质、中缝复合体、蓝斑、多个脑干运动核、下橄榄核、小脑深部核团、前庭核复合体、孤束核、网状结构、背根神经节以及脊髓中数量最多。ORL1 mRNA和结合的广泛分布支持了孤啡肽FQ在多种中枢神经系统功能中发挥广泛作用，包括运动和平衡控制、强化与奖赏、痛觉感受、应激反应、性行为、攻击行为以及生理过程的自主控制。