title: Effects of selective inhibitors of neuronal and inducible NO-synthase on ATP content and survival of cultured rat cerebellar neurons during hyperstimulation of glutamate receptors.
abstract: We studied the effects of selective inhibitors of neuronal and inducible NO-synthase (7-nitroindazole and aminoguanidine) and non-selective NO-synthase inhibitor L-NAME on ATP content and survival of cultured rat cerebellar neurons during hyperstimulation of glutamate receptors with toxic doses of glutamate. Application of 100 μM glutamate reduced ATP content in the primary culture of 7-8- and 14-15-day-old cerebellar granule cells by 66 and 49%, respectively, in comparison with the control. Inhibition of nitric oxide synthesis with 7-nitroindazole during glutamate exposure in the culture of 7-8-day-old neurons and with 7-nitroindazole and aminoguanidine in the culture of 14-15-day-old neurons ensured better protection of cells from ATP level decrease than non-specific inhibition with L-NAME. In addition, inhibition of neuronal and inducible NO-synthase during glutamate exposure decreased death of "young" neurons, whereas death of "old" neurons remained high under these conditions.
authors.affiliation: Laboratory of Membranology, Research Center of Children Health, Russian Academy of Medical Sciences, Moscow, Russia.
authors.forename: M A
authors.initials: MA
authors.lastname: Salykina
authors.forename: E G
authors.initials: EG
authors.lastname: Sorokina
authors.forename: I A
authors.initials: IA
authors.lastname: Krasilnikova
authors.forename: V P
authors.initials: VP
authors.lastname: Reutov
authors.forename: V G
authors.initials: VG
authors.lastname: Pinelis
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D051381:Rats; D017470:Receptors, Glutamate / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D007191:Indazoles; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester