Houtani T, Nishi M, Takeshima H, Sato K, Sakuma S, Kakimoto S, Ueyama T, Noda T, Sugimoto T
Department of Anatomy and Brain Science, Kansai Medical University, Osaka 570-8506, Japan.
J Comp Neurol. 2000 Aug 28;424(3):489-508.
Nociceptin/orphanin FQ (N/OFQ) is an opioid-like heptadecapeptide agonist for the opioid receptor homolog, N/OFQ receptor. To explore the precise distribution of the peptide-receptor system, the authors examined the brain and spinal cord from receptor-deficient mice bearing the targeted mutation (morc(m1)), a lacZ insertional mutation in the N/OFQ receptor gene. Precursor protein N/OFQ (preproN/OFQ) mRNA was detected by using in situ hybridization, and the N/OFQ receptor was detected by using X-gal histochemistry. The N/OFQ receptor reflected by lacZ expression was observed at high levels in the dentate gyrus, lateral septum, subparafascicular thalamic nucleus, medial preoptic area, median preoptic nucleus, ventromedial preoptic nucleus, anterior hypothalamic area, paraventricular hypothalamic nucleus, ventromedial hypothalamic nucleus, auditory brainstem nuclei, pontine dorsal tegmentum, and nucleus of the solitary tract. In situ detection of the N/OFQ receptor mRNA by digoxigenin-labeled riboprobes coupled with tyramide signal amplification in normal and wild-type mice resulted in the regional distribution paralleling the lacZ expression in these regions. PreproN/OFQ mRNA was expressed at high levels in the subparafascicular thalamic nucleus, central gray, central tegmental field, auditory brainstem nuclei, caudal spinal trigeminal nucleus, and spinal dorsal horn. Furthermore, variable levels of expression of the peptide and receptor were seen in distinct sites of the brain and spinal cord. These data indicate a correspondence of the peptide and the receptor in local distribution at limbic, hypothalamic, and brainstem sites. Together with concurrent physiologic and behavioral studies in mutant mice, the results suggest functional roles for the N/OFQ system, including the central regulation of learning and memory, hearing ability, water balance, food intake, and blood pressure.
痛敏肽/孤啡肽FQ（N/OFQ）是一种与阿片受体同源的阿片样十七肽激动剂，作用于N/OFQ受体。为探究该肽-受体系统的精确分布，作者检测了携带靶向突变（morc(m1)）的受体缺陷小鼠的脑和脊髓，该突变是N/OFQ受体基因中的一个lacZ插入突变。采用原位杂交检测前体蛋白N/OFQ（前阿黑皮素原N/OFQ）mRNA，并用X-gal组织化学法检测N/OFQ受体。在齿状回、外侧隔、束旁丘脑下核、内侧视前区、视前正中核、视前腹内侧核、下丘脑前区、下丘脑室旁核、下丘脑腹内侧核、听觉脑干核、脑桥背侧被盖和孤束核中观察到高水平的由lacZ表达反映的N/OFQ受体。在正常和野生型小鼠中，用洋地黄毒苷标记的核糖探针结合酪胺信号放大原位检测N/OFQ受体mRNA，其区域分布与这些区域中的lacZ表达平行。前阿黑皮素原N/OFQ mRNA在束旁丘脑下核、中央灰质、中央被盖区、听觉脑干核、尾侧脊髓三叉神经核和脊髓背角中高水平表达。此外，在脑和脊髓的不同部位可见该肽和受体的表达水平各异。这些数据表明该肽与受体在边缘系统、下丘脑和脑干部位的局部分布具有对应性。结合对突变小鼠进行的同步生理和行为学研究结果提示，N/OFQ系统具有多种功能，包括对学习与记忆、听力、水平衡、食物摄入和血压的中枢调节作用。
