Montiel J L, Cornille F, Roques B P, Noble F
Département de Pharmacochimie Moléculaire et Structurale, U. 266 INSERM-URA D1500 CNRS, UFR des Sciences Pharmaceutiques et Biologiques, Faculté de Pharmacie, Paris, France.
J Neurochem. 1997 Jan;68(1):354-61. doi: 10.1046/j.1471-4159.1997.68010354.x.
The endogenous opioid receptor-like1 (ORL1) ligand, nociceptin/orphanin FQ (FGGFTGARKSARKLANQ), a heptadecapeptide structurally resembling dynorphin A, has recently been identified. The wide distribution of ORL1 mRNA and nociceptin/orphanin FQ precursor in the CNS, particularly in the limbic system regions and in several areas known to be involved in pain perception, suggests that nociceptin/orphanin FQ is potentially endowed with various central functions. In general, activation and/or inactivation of regulatory peptides occur through the action of cell surface peptidases. The physiological mechanisms under which nociceptin/orphanin FQ is metabolized should lead to a better understanding of its physiological functions. Mouse brain cortical slices were incubated in medium containing the heptadecapeptide in the presence or in the absence of peptidase inhibitors. The critical sites of enzymatic cleavage are Phe1-Gly2, Ala7-Arg8, Ala11-Arg12, and Arg12-Lys13 bonds. The major role played by metallopeptidases was confirmed by the complete protection of metabolism in the presence of EDTA. Aminopeptidase N and endopeptidase 24.15 are the two main enzymes involved in nociceptin/orphanin FQ metabolism, whereas endopeptidase 24.11 (involved in enkephalin [YGGFM(L)] catabolism) does not appear critically involved in nociceptin/orphanin FQ metabolism. The physiological relevance of aminopeptidase N and endopeptidase 24.15 in the heptadecapeptide metabolism remains to be determined.
内源性阿片样受体1（ORL1）配体，痛敏肽/孤啡肽FQ（FGGFTGARKSARKLANQ），一种结构上类似于强啡肽A的十七肽，最近已被鉴定出来。ORL1信使核糖核酸和痛敏肽/孤啡肽FQ前体在中枢神经系统中广泛分布，尤其是在边缘系统区域以及几个已知参与痛觉感知的区域，这表明痛敏肽/孤啡肽FQ可能具有多种中枢功能。一般来说，调节肽的激活和/或失活是通过细胞表面肽酶的作用来实现的。痛敏肽/孤啡肽FQ被代谢的生理机制应该有助于更好地理解其生理功能。将小鼠脑皮质切片在含有该十七肽的培养基中孵育，分别添加或不添加肽酶抑制剂。酶切的关键位点是苯丙氨酸1-甘氨酸2、丙氨酸7-精氨酸8、丙氨酸11-精氨酸12和精氨酸12-赖氨酸13键。在乙二胺四乙酸存在的情况下，代谢完全受到保护，这证实了金属肽酶起主要作用。氨肽酶N和内肽酶24.15是参与痛敏肽/孤啡肽FQ代谢的两种主要酶，而参与脑啡肽[YGGFM（L）]分解代谢的内肽酶24.11似乎在痛敏肽/孤啡肽FQ代谢中不起关键作用。氨肽酶N和内肽酶24.15在十七肽代谢中的生理相关性仍有待确定。
