Imaging and therapeutics: the role of neuronal transport in the regional specificity of L-DOPA accumulation in brain.
OBJECTIVE
To investigate the in vitro regional accumulation of L-3,4-dihydroxyphenylalanine (L-DOPA) in brain tissue.


METHODS
Neuronal membrane transport of L-DOPA was investigated in rat and squirrel monkey brain tissue. The kinetics of L-DOPA regional transport was characterized, and the effect of amino acids on transport was evaluated using isolated nerve terminals from striatum and cerebral cortex.


RESULTS
When L-DOPA uptake was measured in modified Krebs-Ringer medium, transport occurred in both synaptosome preparations. In the presence of dilute protein-free plasma, uptake of L-DOPA was significantly present in striatal nerve terminals (P < 0.005), but was completely inhibited in terminals isolated from the cortex. L-DOPA transport in striatal synaptosomes was primarily inhibited by large neutral aromatic L-amino acids, in contrast to that in cortical synaptosomes that was mainly affected by large neutral aliphatic L-amino acids. A saturable component of influx was detected in both synaptosome preparations, where kinetic analysis revealed that the relative affinity of L-DOPA was greater for the carrier in the striatum than in the cortex. Based on the distribution of neuronal cell types within the two regions and the effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioning in squirrel monkeys, the striatal specific accumulation of L-DOPA likely occurs within dopaminergic terminals.


CONCLUSIONS
These results demonstrate that the in vivo regional specificity of L-DOPA localization in brain tissue is primarily controlled by neuronal transport.
Yee
Randa E
RE
Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA, USA
Huang
Sung-Chen
SC
Togasaki
Daniel M
DM
Langston
J William
JW
Satyamurthy
N
N
Barrio
Jorge R
JR