Williams R G, Dockray G J
Neuroscience. 1983 Jul;9(3):563-86. doi: 10.1016/0306-4522(83)90175-6.
The enkephalin-related heptapeptide, Tyr-Gly-Gly-Phe-Met-Arg-Phe, forms the C-terminus of a biosynthetic precursor that contains both Met-enkephalin and Leu-enkephalin sequences. We have studied the distribution of heptapeptide-like immunoreactivity in rat brain by immunohistochemistry using a C-terminal specific antiserum. The results were compared with those obtained using an antiserum specific for the C-terminus of Met-enkephalin which does not react with C-terminally-extended variants. Both antisera specifically stained cell bodies and fibres in many regions of the rat central nervous system. Colchicine was needed for the demonstration of cell bodies with the Met-enkephalin antiserum, but not for the heptapeptide antiserum. In the nucleus of the solitary tract, in the commissural nucleus, the nucleus raphe obscurus and in the hypothalamus, studies of serial sections and re-staining experiments indicated that the two antisera stained the same cell bodies. However, in the olfactory bulb, the anterior olfactory nucleus, the olfactory tubercle, the nucleus accumbens, caudate-putamen, central nucleus of the amygdala, nucleus interstitialis striae terminalis, pre-lateral mamillary nuclei, ventral hypothalamus, hippocampus, peri-aqueductal grey and the granular layer of the cerebellum, cells were stained by the heptapeptide antiserum but not the Met-enkephalin antiserum. The two antisera revealed similar patterns of staining of nerve fibres in many regions including hypothalamus, central nucleus of the amygdala, lateral septum, thalamus, mid-brain and spinal cord. But in other areas notably, pallidum, caudate-putamen, substantia inominata, nucleus of the solitary tract and commissural nucleus, there were abundant fibres and terminals revealed by the Met-enkephalin antiserum but not by the heptapeptide antiserum. The results are discussed with respect to possible patterns of enkephalin biosynthesis; it is suggested that in some neurones immunoreactive enkephalin precursors terminating in the heptapeptide sequence are processed to produce the heptapeptide which is stored in terminals and is available for release as an endogenous opioid agonist in its own right. In other cases, however, it is suggested that the heptapeptide might be cleaved by removal of -Arg-Phe to yield Met-enkephalin which is the primary opioid product of this class of neurone.
脑啡肽相关的七肽,酪氨酸 - 甘氨酸 - 甘氨酸 - 苯丙氨酸 - 甲硫氨酸 - 精氨酸 - 苯丙氨酸,构成了一个生物合成前体的C末端,该前体同时包含甲硫脑啡肽和亮脑啡肽序列。我们使用C末端特异性抗血清,通过免疫组织化学研究了大鼠脑中七肽样免疫反应性的分布。将结果与使用对甲硫脑啡肽C末端特异性的抗血清所获得的结果进行比较,该抗血清不与C末端延伸变体发生反应。两种抗血清均特异性地染色大鼠中枢神经系统许多区域的细胞体和纤维。用甲硫脑啡肽抗血清显示细胞体需要秋水仙碱,但用七肽抗血清则不需要。在孤束核、连合核、中缝隐核和下丘脑中,连续切片研究和复染实验表明,两种抗血清染色相同的细胞体。然而,在嗅球、前嗅核、嗅结节、伏隔核、尾状核 - 壳核、杏仁核中央核、终纹床核间质核、外侧乳头前核、腹侧下丘脑、海马、导水管周围灰质和小脑颗粒层中,细胞被七肽抗血清染色,但未被甲硫脑啡肽抗血清染色。两种抗血清在许多区域包括下丘脑、杏仁核中央核、外侧隔、丘脑、中脑和脊髓中显示出相似的神经纤维染色模式。但在其他区域,特别是苍白球、尾状核 - 壳核、无名质、孤束核和连合核中,甲硫脑啡肽抗血清显示出丰富的纤维和终末,而七肽抗血清则未显示。就脑啡肽生物合成的可能模式对结果进行了讨论;有人提出,在一些神经元中,以七肽序列结尾的免疫反应性脑啡肽前体被加工产生七肽,该七肽储存在终末并可作为内源性阿片样激动剂自行释放。然而,在其他情况下,有人提出七肽可能通过去除 - 精氨酸 - 苯丙氨酸而被切割产生甲硫脑啡肽,甲硫脑啡肽是这类神经元的主要阿片样产物。