title: Blood-brain barrier and neuronal membrane transport of 6-[18F]fluoro-L-DOPA.
abstract: 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.
authors.affiliation: Department of Molecular and Medical Pharmacology, UCLA School of Medicine, B2-086A Center of the Health Sciences, Los Angeles, CA 90095-6948, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Yee
authors.forename: D W
authors.initials: DW
authors.lastname: Cheng
authors.forename: S C
authors.initials: SC
authors.lastname: Huang
authors.forename: M
authors.initials: M
authors.lastname: Namavari
authors.forename: N
authors.initials: N
authors.lastname: Satyamurthy
authors.forename: J R
authors.initials: JR
authors.lastname: Barrio
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D005462:Fluorine Radioisotopes; D007980:Levodopa / Q000493:pharmacokinetics; D008297:Male; D023421:Models, Animal; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005462:Fluorine Radioisotopes; C043437:fluorodopa F 18; D007980:Levodopa; D004295:Dihydroxyphenylalanine