6-cyano-7-nitroquinoxaline-2-3-dione and sapropterin

In this study, the effect of tetrahydrobiopterin deficiency on the nitric oxide/cGMP pathway has been investigated in cerebellar slices derived from the hph-1 mouse. This animal displays a partial deficiency of tetrahydrobiopterin. Basal levels of cGMP were significantly reduced (-29.5%) in the hph-1 mouse cerebellum compared to controls. Following kainate stimulation (500 microM) cGMP levels increased in both control and hph-1 preparations but were again significantly lower (-29.1%) in the hph-1 mouse. Exposure of slices to the nitric oxide donors, S-nitroso-N-acetylpenicillamine and S-nitroso-glutathione, revealed no difference in cGMP accumulation between the two groups. These findings suggest that the cerebellar nitric oxide/cGMP pathway may be impaired in partial tetrahydrobiopterin deficiency states due to diminished nitric oxide formation.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Antioxidants; Biopterins; Cerebellum; Cyclic GMP; Enzyme Inhibitors; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Glutathione; Kainic Acid; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Mutant Strains; Mutation; Nitric Oxide; Nitroarginine; Nitroso Compounds; Organ Culture Techniques; Oxyhemoglobins; Penicillamine; Platelet Aggregation Inhibitors; S-Nitroso-N-Acetylpenicillamine; S-Nitrosoglutathione