Document Detail


Effects of dopamine and L-DOPA on survival of PC12 cells.
MedLine Citation:
PMID:  11002293     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
K Koshimura; J Tanaka; Y Murakami; Y Kato
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  62     ISSN:  0360-4012     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  2000 Oct 
Date Detail:
Created Date:  2000-10-23     Completed Date:  2000-11-30     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  112-9     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Wiley-Liss, Inc.
Affiliation:
First Division, Department of Medicine, Shimane Medical University, Izumo, Japan. kunio@shimane-med.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium / metabolism
Calcium Channel Blockers / pharmacology
Cell Differentiation / drug effects
Cell Survival / drug effects
Culture Media, Serum-Free / pharmacology
Dopa Decarboxylase / antagonists & inhibitors
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
Chemical
Reg. No./Substance:
0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/Calcium Channel Blockers; 0/Culture Media, Serum-Free; 0/Dopamine Uptake Inhibitors; 0/Flavonoids; 0/Levodopa; 0/Monoamine Oxidase Inhibitors; 0/Neuroprotective Agents; 0/Receptors, Dopamine D1; 7440-70-2/Calcium; 9061-61-4/Nerve Growth Factor; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.12.2/Mitogen-Activated Protein Kinase Kinases; EC 4.1.1.-/Dopa Decarboxylase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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