L-3,4-DIHYDROXYPHENYLALANINE INCREASES THE QUANTAL SIZE OF EXOCYTOTICDOPAMINE RELEASE IN-VITRO

The catecholamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) is u sed to augment striatal dopamine (DA), although its mechanism of alter ing 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 cultu res exposed to 40 mM potassium-containing media, L-DOPA (100 mu M for 1 h) increased DA release by > 10-fold, The elevated extracellular DA levels were not significantly blocked by the DA/norepinephrine transpo rt inhibitor nomifensine, demonstrating that reverse transport through catecholamine-uptake carriers plays little role in this release, In P C12 cells, where DA release from individual secretory vesicles can be observed, L-DOPA (50 mu M for 1 h) elevated DA release in high-potassi um media by 370%, Amperometric measurements demonstrated that L-DOPA ( 50 mu M for 40-70 min) did not raise the frequency of vesicular exocyt osis 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 au gmenting cytosolic neurotransmitter, leading to increased quantal size .