Glutamate-induced cell death and formation of radicals can be reduced by lisuride in mesencephalic primary cell culture.
Oxidative stress evoked by excitotoxicity is considered an important factor for the loss of dopaminergic neurons in Parkinson's disease. In vitro, protective effects of the dopamine agonist lisuride on complex I inhibition in primary dopaminergic cell culture have been reported. However, little is known about the effects of lisuride on glutamate-induced radical formation. Here, effects of lisuride on the formation of nitric oxide (NO) and superoxide radicals following glutamate exposure were studied on primary cell cultures prepared from mouse mesencephala. Glutamate treatment resulted in doubling of NO and superoxide radical formation, increased dopaminergic cell degeneration and extensively altered neuronal appearance. Pretreatment with lisuride significantly lowered the levels of either reactive species and increased the survival of dopaminergic neurons compared to glutamate-treated cultures. Moreover, the beneficial effect of lisuride could be completely inhibited by the D2/D3 receptor antagonist sulpiride when co-treated in cultures.
Moldzio
R
R
Institute for Medical Chemistry, DNS, University for Veterinary Medicine, Vienna, Austria. rudolf.moldzio@vu-wien.ac.at
Radad
K
K
Duvigneau
J C
JC
Kranner
B
B
Krewenka
C
C
Piskernik
C
C
Rausch
W D
WD
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004298:Dopamine / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004789:Enzyme Activation / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D005260:Female; D005609:Free Radicals / Q000378:metabolism*; D018698:Glutamic Acid / Q000633:toxicity*; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008090:Lisuride / Q000494:pharmacology*; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D011247:Pregnancy; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors; D013469:Sulpiride / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D000978:Antiparkinson Agents; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018691:Excitatory Amino Acid Antagonists; D005609:Free Radicals; D050637:Receptors, Dopamine D3; D013481:Superoxides; D009569:Nitric Oxide; D019344:Lactic Acid; D018698:Glutamic Acid; D013469:Sulpiride; D008090:Lisuride; D007770:L-Lactate Dehydrogenase; D052248:Nitric Oxide Synthase Type I; D004298:Dopamine