L-3,4-dihydroxyphenylalanine increases the quantal size of exocytotic dopamine release in vitro

J Neurochem. 1996 Feb;66(2):629-36. doi: 10.1046/j.1471-4159.1996.66020629.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Transport / drug effects
  • Cells, Cultured
  • Dopamine / metabolism*
  • Dopamine Agents / pharmacology*
  • Exocytosis*
  • Intracellular Membranes / metabolism
  • Levodopa / pharmacology*
  • Mesencephalon / cytology
  • Mesencephalon / metabolism
  • Neurons / drug effects
  • Neurons / metabolism*
  • PC12 Cells
  • Rats


  • Dopamine Agents
  • Levodopa
  • Dopamine