The fate of perfluoro-tagged metabolites of L-DOPA in mice brains.
The fate of perfluoro-tagged metabolites of L-DOPA in mice brains.
复制标题
L-DOPA 全氟标记代谢物在小鼠大脑中的命运。
DOI：
10.1081/ias-200033834
复制
发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Branch,Craig
中科院分区：
文献类型：
--
作者：
Dingman,Sherry;Mack,David;Branch,Sara;Thomas,Rhys;Guo,Congyuan;Branch,Craig
通过将多个19 F原子标签共价键合到L-DOPA上，产生了一种用于磁共振（MR）成像的新型化合物。标记L-DOPA允许绕过多巴胺（DA）生物合成中的限速因素，即酪氨酸转化为L-DOPA。生物合成途径的下一步是通过L-芳香酸脱羧酶（AADC）去除分子上的羧基，这在L-多巴被神经元吸收后迅速发生。为了在MR成像中用作工具，新化合物和/或其全氟标记的代谢物必须在多巴胺能神经元的囊泡中积累。我们将带有9个19 F原子标记的L-DOPA（250 mg/kg）给予小鼠幼崽，等待1.5或3小时，并使用高压液相色谱法（HPLC）检查神经组织样品中的标记的L-DOPA和标记的DA。L-DOPA的异构体在5位上结合有标记，在腹腔注射后1.5小时转化为标记的DA最高。这项研究提供了第一个直接证据表明，L-DOPA，标记有9个氟原子，被纳入哺乳动物大脑多巴胺能神经元，在那里它被转化为全氟标记的DA。使用这些标记的化合物可能使氟成像研究体内重要神经递质的摄取和转化成为可能。
A novel compound for use in magnetic resonance (MR) imaging was created by covalently bonding multiple19F atom tags toL‐DOPA. TaggingL‐DOPA permits bypassing the rate‐limiting factor in the biosynthesis of dopamine (DA), the conversion of tyrosine intoL‐DOPA. The next step in the biosynthetic pathway, the removal of the carboxyl group on the molecule by the enzymeL‐aromatic acid decarboxylase (AADC), happens rapidly afterL‐DOPA is taken up into neurons. In order to be useful as a tool in MR imaging, the novel compound and/or its perfluoro‐tagged metabolites must accumulate in vesicles in dopaminergic neurons. We administeredL‐DOPA with a nine19F atom tag ( 250 mg/kg) to mice pups, waited 1.5 or 3 hr, and used high pressure liquid chromatography (HPLC) to examine neural tissue samples for taggedL‐DOPA and tagged DA. The isomer ofL‐DOPA with the tag bonded at the 5 position yielded the highest conversion to tagged DA at 1.5 hr after an i.p. injection. This study provides the first direct evidence thatL‐DOPA, tagged with nine fluorine atoms, is taken up into mammalian brain dopaminergic neurons where it is converted to perfluro‐tagged DA. The use of these tagged compounds may make it feasible to investigate the uptake and conversion of important neurotransmitter in vivo with fluorine imaging.