title: Attenuation of oxidative neuronal necrosis by a dopamine D1 agonist in mouse cortical cell cultures.
abstract: 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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Ajou University School of Medicine Suwon, Kyungkido, Korea.
authors.forename: J S
authors.initials: JS
authors.lastname: Noh
authors.forename: B J
authors.initials: BJ
authors.lastname: Gwag
mesh_terms: 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
chemical_list: 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