Panula P, Aarnisalo A A, Wasowicz K
Department of Biology, Abo Akademi University, Turku, Finland.
Prog Neurobiol. 1996 Mar-Apr;48(4-5):461-87. doi: 10.1016/0301-0082(96)00001-9.
Neuropeptide FF (NPFF) and neuropeptide AF (NPAF) are two mammalian amidated neuropeptides which are highly concentrated in the posterior pituitary, spinal cord, hypothalamus and medulla. One precursor protein has been identified in mouse, rat, bovine and human brain. The precursor contains a single copy of both peptides, followed by a glycine residues necessary for amidation and flanked by basic residues necessary for processing by enzymes. In the brain, NPFF-like immunoreactive neurons are found in the hypothalamus and medulla. These systems may be associated with observed effects of NPFF on memory and autonomic regulation, respectively. A hypothalamo-pituitary pathway may be involved in neuroendocrine regulation. This is supported by lack of NPFF in the pituitary gland of vasopressin-deficient Brattleboro rats. It is also possible that NPFF acts as a hormone, as it has been detected in human plasma. The spinal cord contains an intrinsic NPFF-ir neuron system, with cell bodies in the dorsal horn and around the central canal. Nerve terminals are highly concentrated in the superficial laminae of the dorsal horn, where NPFF-immunoreactivity can be released by, e.g., potassium and substance P. One specific high-affinity binding site, distinct from binding sites for other peptides, has been characterized in the rat and human brain and spinal cord. The NPFF receptor appears to be coupled to a G-protein, but details of the second messenger systems have not been clarified yet. Intracerebroventricular injection of NPFF induces a vigorous abstinence syndrome in morphine-tolerant rats. Although clear antiopioid-like effects of NPFF on pain have been observed, some studies have also demonstrated long-lasting analgesic effects. These findings and the observed increase in NPFF-immunoreactivity in the cerebrospinal fluid during development of opiate tolerance render NPFF an interesting and challenging target of investigation.
神经肽FF（NPFF）和神经肽AF（NPAF）是两种哺乳动物酰胺化神经肽，在垂体后叶、脊髓、下丘脑和延髓中高度集中。在小鼠、大鼠、牛和人类大脑中已鉴定出一种前体蛋白。该前体包含这两种肽的单拷贝，随后是酰胺化所需的甘氨酸残基，并由酶加工所需的碱性残基侧翼包围。在大脑中，下丘脑和延髓中发现了NPFF样免疫反应性神经元。这些系统可能分别与NPFF对记忆和自主调节的观察到的作用相关。下丘脑 - 垂体途径可能参与神经内分泌调节。这得到了抗利尿激素缺乏的布拉德福德大鼠垂体中缺乏NPFF的支持。NPFF也有可能作为一种激素起作用，因为它已在人类血浆中被检测到。脊髓含有一个内在的NPFF免疫反应性神经元系统，其细胞体位于背角和中央管周围。神经末梢高度集中在背角的浅层，在那里NPFF免疫反应性可以通过例如钾和P物质释放。在大鼠和人类大脑及脊髓中已鉴定出一个与其他肽的结合位点不同的特异性高亲和力结合位点。NPFF受体似乎与一种G蛋白偶联，但第二信使系统的细节尚未阐明。脑室内注射NPFF会在吗啡耐受的大鼠中诱发强烈的戒断综合征。尽管已观察到NPFF对疼痛有明显的抗阿片样作用，但一些研究也证明了其持久的镇痛作用。这些发现以及在阿片耐受发展过程中脑脊液中NPFF免疫反应性增加的观察结果，使NPFF成为一个有趣且具有挑战性的研究靶点。
