[Change of the nitric oxide synthase activity after administration of neurotoxic compounds in mice].
The possible contribution of reactive oxygen and nitrogen species (RONS) to the development of the neurode-generation came up after the investigations with neurotoxic compounds. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (METH) have detrimental effect on the dopaminergic neurons. The aim of our study was to examine whether altered nitric oxide synthase (NOS) enzyme activity can be involved in the damage induced by these neurotoxins. The other goal of the study was to investigate the applicability of the measurement of the ratio of NADP+/L-citrulline formed by the enzyme to assess the coupled state of the NOS. Elevated NOS activity in mouse striatum and declined enzyme activity in mouse hippocampus have been found after administration of MPTP Decreased NOS activity in mouse striatum and hippocampus was observed after administration of METH. The ratio of the NADP+/L-citrulline produced by the enzyme provides useful information about the coupling state of the NOS. The ratio in the presence of saturating substrate concentration measured in our experiments was comparable with the data found in the literature. Dramatically increased ratio could be observed in case of decreasing substrate concentration indicating the uncoupled function of the enzyme.
Halász
Attila Sándor
AS
Semmelweis Egyetem, Gyógyszerhatástani Intézet, Budapest.
Pálfi
Melinda
M
Tábi
Tamás
T
Magyar
Kálman
K
Szöko
Eva
E
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D002956:Citrulline / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009249:NADP / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*
D009498:Neurotoxins; D002956:Citrulline; D008694:Methamphetamine; D009249:NADP; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D019001:Nitric Oxide Synthase