Weitz C J, Faull K F, Goldstein A
Addiction Research Foundation, Palo Alto, California 94304.
Nature. 1987;330(6149):674-7. doi: 10.1038/330674a0.
The possibility that morphine could be synthesized in animals has long been considered and a pathway in mammalian brain analogous to that in the opium poppy has been proposed. Substances have been detected in mammalian brain that are recognized by antisera raised against morphine. Recently we reported the presence of three such immunoreactive substances in bovine hypothalamus and adrenal, and in rat brain, and the definitive identification of two of them by gas chromatography-mass spectrometry as morphine and codeine. Incorporation of a labelled precursor has demonstrated the biosynthesis of morphine in the opium poppy from tyrosine-derived units (see Fig. 1). Intramolecular coupling of reticuline to form salutaridine is the critical step that generates the morphine skeleton (morphinan) and the stereochemistry of the morphinan series. We now report the conversion in vivo and in vitro of reticuline to salutaridine by rat liver, but this conversion is not detectable in rat brain and bovine adrenal. This is the first direct demonstration of the synthesis of a morphinan in an animal tissue and also supports the hypothesis that morphine and codeine in brain and adrenal are of endogenous origin.
长期以来，人们一直认为动物体内有可能合成吗啡，并且有人提出哺乳动物大脑中存在一条类似于罂粟中的合成途径。在哺乳动物大脑中已检测到一些物质，它们能被针对吗啡产生的抗血清识别。最近，我们报道了在牛下丘脑、肾上腺以及大鼠大脑中存在三种此类免疫反应性物质，并通过气相色谱 - 质谱法明确鉴定其中两种为吗啡和可待因。掺入标记前体已证明罂粟中吗啡是由酪氨酸衍生单元生物合成的（见图1）。网状番荔枝碱分子内偶联形成去甲乌药碱是生成吗啡骨架（吗啡喃）以及吗啡喃系列立体化学的关键步骤。我们现在报道大鼠肝脏能在体内和体外将网状番荔枝碱转化为去甲乌药碱，但在大鼠大脑和牛肾上腺中未检测到这种转化。这是首次在动物组织中直接证明吗啡喃的合成，也支持了大脑和肾上腺中吗啡和可待因是内源性的这一假说。
