Farah M B, Adler-Graschinsky E, Langer S Z
Naunyn Schmiedebergs Arch Pharmacol. 1977 Mar;297(2):119-31. doi: 10.1007/BF00499921.
The hypothalamus, the cerebral cortex and the cerebellar cortex of the rat were labelled in vitro with 3H-noradrenaline (3H-NA) and the metabolism of the tritiated transmitter was studied during spontaneous outflow and under conditions of release elicited by exposure to 20 mM K+. In the three areas of the central nervous system of the rat 3H-NA accounted for approximately 40% of the total radioactivity in spontaneous outflow while the 3H-O-methylated deaminated fraction (3H-OMDA) and 3H-3,4-dihydroxyphenylglycol (3H-DOPEG) were the main metabolites. Exposure to the reserpine-like agent, Ro 4-1284 induced a selective increase in the spontaneous outflow of 3H-DOPEG, while the contribution of the 3H-OMDA metabolites to the release induced by Ro 4-1284 was very small. During 3H-transmitter release elicited by exposure to 20 mM K+, approximately 80% of the radioactivity was collected as unmetabolized 3H-NA, while 3H-DOPEG was the main metabolite formed under these experimental conditions. Exposure to cocaine prevented 3H-DOPEG formation from 3H-NA released by K+, indicating that 3H-DOPEG was formed after neuronal reuptake of the transmitter released by K+. After in vitro labelling with 3H-NA, the unmetabolized transmitter represented approximately 70% of the total radioactivity retained in the tissue. However, when 3H-NA was administered in vivo, by intraventricular injection, only 30% of the total radioactivity retained by the tissue was accounted for by 3H-NA, and 60% of the radioactivity corresponded to the 3H-OMDA fraction, most of which was retained as 3H-MOPEG sulfate. When the rats were pretreated with pyrogallol, free 3H-DOPEG accounted for nearly 50% of the radioactivity retained in the three areas of the central nervous system after in vivo labelling with 3H-NA. When monoamine oxidase was inhibited by pargyline and 3H-NA was administered by intraventricular injection, 3H-NMN accounted for approximately 50% of the total radioactivity retained in the three areas of the central nervous system of the rat. The results obtained are compatible with the view that formation of the deamined glycol is the first step in the metabolism of 3H-NA in the rat central nervous system. In addition, it is concluded that the determination of the levels of some NA metabolites retained in the central nervous system does not necessarily represent an accurate reflection of the degree of central noradrenergic activity or of selective metabolic pathways. Consequently, in studies on the metabolism of NA it is important to take into account not only the transmitter and its metabolites in the tissue but also in the outflow from the structures studied either under in vivo or in vitro conditions.
用3H-去甲肾上腺素（3H-NA）对大鼠的下丘脑、大脑皮层和小脑皮层进行体外标记，并研究了在自发释放以及暴露于20 mM K+引发释放的条件下，氚标记递质的代谢情况。在大鼠中枢神经系统的这三个区域中，3H-NA在自发释放中占总放射性的约40%，而3H-O-甲基化脱胺部分（3H-OMDA）和3H-3,4-二羟基苯乙二醇（3H-DOPEG）是主要代谢产物。暴露于利血平样药物Ro 4-1284会导致3H-DOPEG的自发释放选择性增加，而3H-OMDA代谢产物对Ro 4-1284诱导的释放贡献非常小。在暴露于20 mM K+引发3H-递质释放期间，约80%的放射性以未代谢的3H-NA形式收集，而3H-DOPEG是在这些实验条件下形成的主要代谢产物。暴露于可卡因可阻止K+释放的3H-NA形成3H-DOPEG，表明3H-DOPEG是在神经元重新摄取K+释放的递质后形成的。用3H-NA进行体外标记后，未代谢的递质占组织中保留的总放射性的约70%。然而，当通过脑室内注射在体内给予3H-NA时，组织保留的总放射性中只有30%由3H-NA构成，60%的放射性对应于3H-OMDA部分，其中大部分以3H-硫酸甲氧去甲肾上腺素的形式保留。当大鼠用焦性没食子酸预处理后，在用3H-NA进行体内标记后，游离的3H-DOPEG在中枢神经系统的这三个区域中占保留放射性的近50%。当用优降宁抑制单胺氧化酶并通过脑室内注射给予3H-NA时，3H-NMN在大鼠中枢神经系统的这三个区域中占保留总放射性的约50%。所得结果与以下观点一致，即脱胺二醇的形成是大鼠中枢神经系统中3H-NA代谢的第一步。此外，得出的结论是，测定中枢神经系统中保留的某些NA代谢产物的水平不一定能准确反映中枢去甲肾上腺素能活性的程度或选择性代谢途径。因此，在关于NA代谢的研究中，重要的是不仅要考虑组织中的递质及其代谢产物，还要考虑在体内或体外条件下所研究结构的流出物中的情况。
