Protection of dopaminergic neurons in primary culture by lisuride.
Dopamine agonists play an important role in the treatment of Parkinson's disease by reducing the administration of L-3,4-dihydroxyphenylalanine (L-DOPA). The enzymatic and non-enzymatic conversion of L-DOPA is suspected to increase oxidative stress, which leads to the degeneration of dopaminergic neurons in Parkinson's disease. In primary mouse mesencephalic cultures we show that the dopamine D1/D2 receptor agonist lisuride, in a concentration range of 0.001-1 microM, enhances the survival of dopaminergic neurons, protects against toxicity induced by L-DOPA or 1-methyl-4-phenylpyridinium ion (MPP+) and stimulates 3H-dopamine uptake. Lisuride also reduces anaerobic metabolism during incubation with L-DOPA. The present findings suggest that lisuride may have trophic/survival-promoting properties and potentially reduces oxidative stress.
Gille
G
G
Department of Neurology, Technical University of Dresden, Federal Republic of Germany. gabigille@yahoo.com
Rausch
W D
WD
Hung
S T
ST
Moldzio
R
R
Ngyuen
A
A
Janetzky
B
B
Engfer
A
A
Reichmann
H
H
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology* / Q000633:toxicity; D002478:Cells, Cultured; D019610:Cytoprotection; D004298:Dopamine / Q000502:physiology*; D007980:Levodopa / Q000633:toxicity; D008090:Lisuride / Q000494:pharmacology*; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*
D000978:Antiparkinson Agents; D007980:Levodopa; D008090:Lisuride; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine