Allard M, Zajac J M, Simonnet G
Unité de Neurobiologie Intégrative, INSERM U.176 Université de Bordeaux II, France.
Neuroscience. 1992 Jul;49(1):101-16. doi: 10.1016/0306-4522(92)90078-g.
The neuropeptide FLFQPQRFamide is a structure related to FMRFamide which is able to inhibit the effects of both endogenous and exogenous opiates. This morphine-modulating activity is mediated via the stimulation of specific FLFQPQRFamide receptors, different from opiate receptors. In vitro quantitative receptor autoradiography was performed on frozen sections of rat central nervous system to characterize binding properties and visualize FLFQPQRFamide receptors using the specific ligand [125I]YLFQPQRFamide, a radio-iodinated analogue of FLFQPQRFamide. [125I]YLFQPQRFamide appeared to interact reversibly with a single class of binding sites (KD = 0.2 nM). The specific binding represented 80% of the total binding at 0.05 nM, the FLFQPQRFamide concentration used in this mapping study. Sites labelled with [125I]YLFQPQRFamide were distributed heterogeneously within the brain and spinal cord. A high density of FLFQPQRFamide binding sites was detected in the most external layers of the dorsal horn of spinal cord and various nuclei of pons and medulla including trigeminal, dorsal tegmental and reticular nuclei. Nucleus of solitary tract, parabrachial, ambiguous and facial nuclei are also intensively labelled. Some structures of mesencephalon and diencephalon exhibited a high density of FLFQPQRFamide binding sites: central gray, raphe nuclei and thalamic nuclei such as parafascicular, laterodorsal, central median, paratenial and paraventricular nuclei. Suprachiasmatic and mammillary nuclei, lateral, posterior and anterior areas of hypothalamus and medial preoptic area exhibited high labelling. FLFQPQRFamide binding sites were also seen in some structures of the dopaminergic meso-cortico-limbic system including ventral tegmental area, cingulate cortex, lateral septum and the head of the caudate-putamen. Dense labelling appeared in the presubiculum of hippocampus. The dissimilar mapping of FLFQPQRFamide and opiate brain receptors confirms our previous pharmacological findings in FLFQPQRFamide binding studies on rat spinal cord membranes, showing that FLFQPQRFamide receptors are different from opiate receptors. There was a good correspondence between localization of binding sites and that of the putative endogenous peptide. Both occur in brain areas previously associated with analgesic action of opiates. However, the mapping of FLFQPQRFamide receptors in the central nervous system suggests that the FLFQPQRFamide system could be implicated in other physiological functions.
神经肽FLFQPQRFamide是一种与FMRFamide结构相关的物质，它能够抑制内源性和外源性阿片类药物的作用。这种吗啡调节活性是通过刺激特定的FLFQPQRFamide受体介导的，这些受体与阿片受体不同。利用特异性配体[125I]YLFQPQRFamide（一种FLFQPQRFamide的放射性碘化类似物），对大鼠中枢神经系统的冰冻切片进行体外定量受体放射自显影，以表征结合特性并可视化FLFQPQRFamide受体。[125I]YLFQPQRFamide似乎与一类单一的结合位点发生可逆性相互作用（解离常数KD = 0.2 nM）。在本图谱研究中使用的FLFQPQRFamide浓度为0.05 nM时，特异性结合占总结合的80%。用[125I]YLFQPQRFamide标记的位点在脑和脊髓中分布不均。在脊髓背角的最外层以及脑桥和延髓的各种核团中检测到高密度的FLFQPQRFamide结合位点，包括三叉神经核、背侧被盖核和网状核。孤束核、臂旁核、疑核和面神经核也被强烈标记。中脑和间脑的一些结构表现出高密度的FLFQPQRFamide结合位点：中央灰质、中缝核以及丘脑核团，如束旁核、外侧背核、中央中核、旁中央核和室旁核。视交叉上核和乳头体核、下丘脑的外侧、后部和前部区域以及内侧视前区显示出高标记。在多巴胺能中脑 - 皮质 - 边缘系统的一些结构中也发现了FLFQPQRFamide结合位点，包括腹侧被盖区、扣带回皮质、外侧隔以及尾状 - 壳核头部。海马的前下托出现密集标记。FLFQPQRFamide和阿片类脑受体的不同图谱证实了我们之前在大鼠脊髓膜上进行FLFQPQRFamide结合研究的药理学发现，表明FLFQPQRFamide受体与阿片受体不同。结合位点的定位与假定的内源性肽的定位之间存在良好的对应关系。两者都出现在先前与阿片类药物镇痛作用相关的脑区。然而，中枢神经系统中FLFQPQRFamide受体的图谱表明，FLFQPQRFamide系统可能参与其他生理功能。
