Effects of dopamine and L-DOPA on survival of PC12 cells

The effects of dopamine and L-DOPA on survival were examined in differentia ted PC12 cells. Addition of dopamine to the culture medium at 3-30 mu M pre vented cell death induced by depletion of serum and nerve growth factor (NG F). At 100 mu M, dopamine induced cell death. The cell-protective effect of dopamine was not affected by nomifensine, an inhibitor of dopamine uptake, or pargyline, an inhibitor of monoamine oxidase, suggesting that dopamine is working outside the cell. The cell-protective effect of dopamine was blu nted by SCH-23390, a D-1 antagonist, but not sulpiride, a D-1 antagonist, i ndicating that the cell protective effect of dopamine is mediated by D-1 re ceptors in PC12 cells. L-DOPA also protected PC12 cells from cell death ind uced by depletion of serum and NGF at low concentrations and showed toxicit y at high concentration. The effect of L-DOPA was unchanged after inhibitio n of conversion of L-DOPA to dopamine by m-hydroxybenzylhydrazine (NSD-1015 ), an inhibitor of DOPA decarboxylase, suggesting that L-DOPA itself is wor king for cell protection. Intracellular Ca2+ concentration and mitogen-acti vated protein (MAP) kinase activity were increased by both dopamine and L-D OPA. The effects of dopamine and L-DOPA on cell survival were blunted by ni cardipine, a Ca2+ channel blocker, and PD-98059, an inhibitor of MAP kinase kinase (MEK). These results taken together raised the possibility that dop amine and L-DOPA protect PC12 cells from cell death at low concentrations b y activating MAP kinase activity via elevation of intracellular Ca2+ concen tration. (C) 2000 Wiley-Liss, Inc.