Ikeda K, Watanabe M, Ichikawa T, Kobayashi T, Yano R, Kumanishi T
Laboratory for Cellular Information Processing, Brain Science Institute, RIKEN, Wako, Saitama, Japan.
J Comp Neurol. 1998 Sep 14;399(1):139-51. doi: 10.1002/(sici)1096-9861(19980914)399:1<139::aid-cne11>3.0.co;2-c.
Nociceptin/orphanin FQ (N/OFQ) and its receptor share similarities to opioids and their receptors in terms of the molecular structure and signaling pathway, but the two systems exhibit different actions in vivo. To understand the mechanism of N/OFQ-system actions, we examined, by in situ hybridization analysis, the distribution of preproN/OFQ and N/OFQ receptor mRNAs in the developing and adult mouse central nervous systems (CNS). In most neural regions, preproN/OFQ mRNA was mainly expressed in a small population of middle-sized neurons. These neurons were scattered between large projection-type neurons or within the neuropil, suggestive of interneurons. In some other nuclei (lateral septum, bed nucleus of the stria terminalis, reticular thalamic nucleus, inferior colliculus, and rostral periolivery nucleus), preproN/OFQ mRNA was expressed in a number of large projection-type neurons. By contrast, N/OFQ receptor mRNA was evenly expressed in most neurons of the adult CNS. Considering the inhibitory actions of N/OFQ, the distinct cellular expression pattern of the N/OFQ system suggests that the release of N/OFQ from interneurons may lower neuronal and synaptic activities of neighboring neurons, leading to integration or modulation of local circuits. Furthermore, the cellular expression pattern, distinct from that of the opioid system, may provide a possible molecular/cellular basis for the different in vivo actions of N/OFQ and opioids. In embryonic stages, both preproN/OFQ and N/OFQ receptor mRNAs were highly and widely expressed in the mantle zone, suggesting the possible importance of N/OFQ signaling in CNS development.
痛敏肽/孤啡肽FQ（N/OFQ）及其受体在分子结构和信号通路方面与阿片类物质及其受体存在相似性，但这两个系统在体内表现出不同的作用。为了解N/OFQ系统作用的机制，我们通过原位杂交分析，研究了前体N/OFQ和N/OFQ受体mRNA在发育中和成年小鼠中枢神经系统（CNS）中的分布。在大多数神经区域，前体N/OFQ mRNA主要在一小群中等大小的神经元中表达。这些神经元散布在大型投射型神经元之间或神经毡内，提示为中间神经元。在其他一些核团（外侧隔核、终纹床核、丘脑网状核、下丘和吻侧橄榄周核）中，前体N/OFQ mRNA在一些大型投射型神经元中表达。相比之下，N/OFQ受体mRNA在成年CNS的大多数神经元中均匀表达。考虑到N/OFQ的抑制作用，N/OFQ系统独特的细胞表达模式表明，中间神经元释放的N/OFQ可能会降低相邻神经元的神经元和突触活动，从而导致局部回路的整合或调节。此外，这种与阿片类系统不同的细胞表达模式，可能为N/OFQ和阿片类物质在体内不同的作用提供了一个可能的分子/细胞基础。在胚胎阶段，前体N/OFQ和N/OFQ受体mRNA在套层中均高度且广泛表达，提示N/OFQ信号在CNS发育中可能具有重要作用。
