title: Protective effects of nicotine against aminochrome-induced toxicity in substantia nigra derived cells: implications for Parkinson's disease.
abstract: Parkinson's disease is a debilitating progressive neurodegenerative disorder that results from the loss of or damage to dopaminergic cells containing neuromelanin in the substantia nigra (SN). The underlying neurodegenerative mechanism(s), however, remain elusive. Aminochrome, the precursor of neuromelanin is an endogenous substance capable of inducing selective neurotoxicity to dopaminergic neurons in SN. Nicotine, on the other hand, may offer protective effects against dopaminergic cell damage induced by various neurotoxins including MPTP and salsolinol. In this study, we sought to determine whether nicotine may also protect against aminochrome-induced toxicity in SN derived RCSN-3 cells. Exposure of RCSN-3 cells to a combination of aminochrome (50 μM) and dicoumarol (50 μM) for 48 h induced approximately 70 % cell death. Pretreatment with nicotine, dose-dependently blocked this toxicity. The effects of nicotine in turn were dose-dependently blocked by mecamylamine, a non-selective nicotinic receptor antagonist. These results suggest involvement of nicotinic receptors in protective effects of nicotine against aminochrome-induced toxicity and provide further evidence for possible therapeutic effects of nicotine or nicotinic agonists in Parkinson's disease.
authors.affiliation: Department of Molecular & Clinical Pharmacology, Faculty of Medicine, ICBM, University of Chile, Santiago, Chile.
authors.forename: Patricia
authors.initials: P
authors.lastname: Muñoz
authors.forename: Sandro
authors.initials: S
authors.lastname: Huenchuguala
authors.forename: Irmgard
authors.initials: I
authors.lastname: Paris
authors.forename: Carlos
authors.initials: C
authors.lastname: Cuevas
authors.forename: Monica
authors.initials: M
authors.lastname: Villa
authors.forename: Pablo
authors.initials: P
authors.lastname: Caviedes
authors.forename: Juan
authors.initials: J
authors.lastname: Segura-Aguilar
authors.forename: Yousef
authors.initials: Y
authors.lastname: Tizabi
mesh_terms: D000818:Animals; D002460:Cell Line; D001728:Dicumarol / Q000633:toxicity; D059290:Dopaminergic Neurons / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D045563:Indolequinones / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008464:Mecamylamine / Q000494:pharmacology; D008543:Melanins / Q000378:metabolism; D009538:Nicotine / Q000627:therapeutic use*; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000473:pathology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D014475:Uncoupling Agents / Q000633:toxicity
chemical_list: D045563:Indolequinones; D008543:Melanins; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D014475:Uncoupling Agents; C014121:neuromelanin; C091584:aminochrome 1; D008464:Mecamylamine; D009538:Nicotine; D001728:Dicumarol