Yee R E, Cheng D W, Huang S C, Namavari M, Satyamurthy N, Barrio J R
Department of Molecular and Medical Pharmacology, UCLA School of Medicine, B2-086A Center of the Health Sciences, Los Angeles, CA 90095-6948, USA.
Biochem Pharmacol. 2001 Nov 15;62(10):1409-15. doi: 10.1016/s0006-2952(01)00787-0.
The transport of 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]FDOPA) across the blood-brain barrier (BBB) and neuronal membranes was compared with that of L-3,4-dihydroxyphenylalanine (L-DOPA) in rats. The carotid injection method was used as a direct measurement of [18F]FDOPA, 1-[14C]-L-DOPA, and 3-[14C]-L-DOPA transport across the BBB, while isolated nerve terminals were used to examine neuronal membrane transport of [3H]-L-DOPA. [18F]FDOPA appeared to use the same large neutral amino acid carrier for BBB transport as L-DOPA and L-phenylalanine. In addition, carbidopa [L-alpha-hydrazino-alpha-methyl-beta-(3,4-dihydroxyphenyl)propionic acid] was found not to have direct interference with the transport carrier on the BBB, but indirectly inhibited aromatic L-amino acid decarboxylase (AAAD) activity in brain endothelium by depletion of pyridoxal phosphate, a necessary cofactor of the enzyme. In striatal and cortical synaptosomes, [3H]-L-DOPA uptake was inhibited by non-radioactive L-DOPA, FDOPA, and 6-fluoro-L-meta-tyrosine (6-FMT). The inhibition was significantly greater in terminals isolated from the striatum than in those from the cerebral cortex. FDOPA, 6-FMT, and L-DOPA equally inhibited the neuronal transport of [3H]-L-DOPA. This suggests that FDOPA and 6-FMT compete with L-DOPA at similar transport sites at the neuronal membrane.
在大鼠中，将6-[18F]氟-L-3,4-二羟基苯丙氨酸（[18F]FDOPA）跨血脑屏障（BBB）和神经元膜的转运与L-3,4-二羟基苯丙氨酸（L-DOPA）的转运进行了比较。采用颈动脉注射法直接测量[18F]FDOPA、1-[14C]-L-DOPA和3-[14C]-L-DOPA跨BBB的转运，同时使用分离的神经末梢来检测[3H]-L-DOPA的神经元膜转运。[18F]FDOPA似乎与L-DOPA和L-苯丙氨酸使用相同的大中性氨基酸载体进行BBB转运。此外，发现卡比多巴[L-α-肼基-α-甲基-β-(3,4-二羟基苯基)丙酸]对BBB上的转运载体没有直接干扰，但通过消耗磷酸吡哆醛（该酶的必需辅因子）间接抑制脑内皮中的芳香族L-氨基酸脱羧酶（AAAD）活性。在纹状体和皮质突触体中，非放射性L-DOPA、FDOPA和6-氟-L-间酪氨酸（6-FMT）抑制了[3H]-L-DOPA的摄取。纹状体分离的末梢中的抑制作用明显大于大脑皮质分离的末梢中的抑制作用。FDOPA、6-FMT和L-DOPA同等程度地抑制了[3H]-L-DOPA的神经元转运。这表明FDOPA和6-FMT在神经元膜的相似转运位点与L-DOPA竞争。
