Attenuation of oxidative neuronal necrosis by a dopamine D1 agonist in mouse cortical cell cultures.
Events which lead to an increase in intracellular free radicals induce necrotic cell death of cultured cortical neurons. In the present study, we report that treatment with 1 microM (+/-)-SKF-38393 hydrochloride, a selective D1 agonist, as well as 100 microM trolox, a lipophilic vitamin E analogue, significantly prevented oxidative-related necrotic cell death following exposure to 10 microM Fe2+ or 1 mM buthionine sulfoximine, an inhibitor of gamma-glutamylcysteine synthetase. The neuroprotective effect of (+/-)-SKF-38393 hydrochloride was partially reversed by addition of (+/-)-SKF-83566 hydrochloride, a selective D1 antagonist. Quinelorane dihydrochloride, a selective D2 agonist, did not influence free radical neurotoxicity. Interestingly, inclusion of (+/-)-SKF-38393 hydrochloride or quinelorane dihydrochloride did not attenuate apoptotic cell death of cortical neurons deprived of serum. The present study provides evidence that (+/-)-SKF-38393 hydrochloride attenuates oxidative neuronal necrosis, which has unique therapeutic potential for the treatment of various neurodegenerative diseases linked to oxidative stress.
Noh
J S
JS
Department of Psychiatry and Behavioral Sciences, Ajou University School of Medicine Suwon, Kyungkido, Korea.
Gwag
B J
BJ
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D002839:Chromans / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D051379:Mice / Q000196:embryology; D009336:Necrosis; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010084:Oxidation-Reduction; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D014810:Vitamin E / Q000031:analogs & derivatives
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000975:Antioxidants; D002839:Chromans; D016895:Culture Media, Serum-Free; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018696:Neuroprotective Agents; D017447:Receptors, Dopamine D1; D014810:Vitamin E; C044846:SKF83566; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid