RRC ID 71719
Author Koshimura K, Tanaka J, Murakami Y, Kato Y.
Title Effects of dopamine and L-DOPA on survival of PC12 cells.
Journal J Neurosci Res
Abstract The effects of dopamine and L-DOPA on survival were examined in differentiated PC12 cells. Addition of dopamine to the culture medium at 3-30 microM prevented cell death induced by depletion of serum and nerve growth factor (NGF). At 100 microM, 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 blunted by SCH-23390, a D(1) antagonist, but not sulpiride, a D(2) antagonist, indicating that the cell protective effect of dopamine is mediated by D(1) receptors in PC12 cells. L-DOPA also protected PC12 cells from cell death induced by depletion of serum and NGF at low concentrations and showed toxicity at high concentration. The effect of L-DOPA was unchanged after inhibition of conversion of L-DOPA to dopamine by m-hydroxybenzylhydrazine (NSD-1015), an inhibitor of DOPA decarboxylase, suggesting that L-DOPA itself is working for cell protection. Intracellular Ca(2+) concentration and mitogen-activated protein (MAP) kinase activity were increased by both dopamine and L-DOPA. The effects of dopamine and L-DOPA on cell survival were blunted by nicardipine, a Ca(2+) channel blocker, and PD-98059, an inhibitor of MAP kinase kinase (MEK). These results taken together raised the possibility that dopamine and L-DOPA protect PC12 cells from cell death at low concentrations by activating MAP kinase activity via elevation of intracellular Ca(2+) concentration.
Volume 62(1)
Pages 112-9
Published 2000-10-1
DOI 10.1002/1097-4547(20001001)62:1<112::AID-JNR12>3.0.CO;2-6
PII 10.1002/1097-4547(20001001)62:1<112::AID-JNR12>3.0.CO;2-6
PMID 11002293
MeSH Animals Aromatic Amino Acid Decarboxylase Inhibitors Calcium / metabolism Calcium Channel Blockers / pharmacology Cell Differentiation / drug effects Cell Survival / drug effects Culture Media, Serum-Free / pharmacology Dopamine / pharmacology* Dopamine Uptake Inhibitors / pharmacology Dose-Response Relationship, Drug Flavonoids / pharmacology Intracellular Fluid / metabolism Levodopa / pharmacology* Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors Mitogen-Activated Protein Kinases / metabolism Monoamine Oxidase Inhibitors / pharmacology Nerve Growth Factor / pharmacology Neuroprotective Agents / pharmacology PC12 Cells Rats Receptors, Dopamine D1 / antagonists & inhibitors
IF 4.699
Human and Animal Cells PC-12(RCB0009)