Pergolide protects dopaminergic neurons in primary culture under stress conditions.
Dopamine agonists are an important therapeutic strategy in the treatment of Parkinson's disease. They postpone the necessity for and reduce the required dose of L-3,4-dihydroxyphenylalanine (L-DOPA) medication thus protecting against the development of motor complications and potential oxidative stress due to L-DOPA metabolism. In primary cultures from mouse mesencephalon we show that pergolide, a preferential D(2) agonist enhanced the survival of healthy dopaminergic neurons at low concentrations of 0.001 microM. About 100 fold higher concentrations (0.1 microM) were necessary to partially reverse the toxic effects of 10 microM 1-methyl-4-phenylpyridinium (MPP(+)). Pergolide was equally effective in preventing the reduction of dopamine uptake induced by 200 microM L-DOPA. Furthermore, between 0.001-0.1 microM it also reduced lactate production thus promoting aerobic metabolism. The present findings suggest that pergolide protects dopaminergic neurons under conditions of elevated 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
Janetzky
B
B
Hundemer
H P
HP
Kolter
T
T
Reichmann
H
H
D015655:1-Methyl-4-phenylpyridinium / Q000037:antagonists & inhibitors / Q000506:poisoning; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism* / Q000493:pharmacokinetics; D015259:Dopamine Agents / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology; D008636:Mesencephalon / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010479:Pergolide / Q000494:pharmacology*; D013312:Stress, Physiological / Q000503:physiopathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015259:Dopamine Agents; D018491:Dopamine Agonists; D018696:Neuroprotective Agents; D010479:Pergolide; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine