L-3,4-dihydroxyphenylalanine increases the quantal size of exocytotic dopamine release in vitro.
The catecholamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) is used to augment striatal dopamine (DA), although its mechanism of altering neurotransmission is not well understood. We observed the effects of L-DOPA on catecholamine release in ventral midbrain neuron and PC12 pheochromocytoma cell line cultures. In ventral midbrain neuron cultures exposed to 40 mM potassium-containing media, L-DOPA (100 microM for 1 h) increased DA release by > 10-fold. The elevated extracellular DA levels were not significantly blocked by the DA/norepinephrine transport inhibitor nomifensine, demonstrating that reverse transport through catecholamine-uptake carriers plays little role in this release. In PC12 cells, where DA release from individual secretory vesicles can be observed, L-DOPA (50 microM for 1 h) elevated DA release in high-potassium media by 370%. Amperometric measurements demonstrated that L-DOPA (50 microM for 40-70 min) did not raise the frequency of vesicular exocytosis but increased the average size of quantal release to at least 250% of control levels. Together, these findings suggest that L-DOPA can increase stimulation-dependent transmitter release from DA cells by augmenting cytosolic neurotransmitter, leading to increased quantal size.
Pothos
E
E
Department of Neuroscience, New York State Psychiatric Institute, New York, USA.
Desmond
M
M
Sulzer
D
D
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D005089:Exocytosis; D007425:Intracellular Membranes / Q000378:metabolism; D007980:Levodopa / Q000494:pharmacology*; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats
D015259:Dopamine Agents; D007980:Levodopa; D004298:Dopamine