Impairment of the nitric oxide/cyclic GMP pathway in cerebellar slices prepared from the hph-1 mouse

Brain Res. 1996 Sep 30;735(1):169-72. doi: 10.1016/0006-8993(96)00892-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Animals
  • Antioxidants / metabolism
  • Biopterins / analogs & derivatives
  • Biopterins / biosynthesis
  • Biopterins / deficiency
  • Biopterins / genetics
  • Cerebellum / drug effects
  • Cerebellum / metabolism*
  • Cyclic GMP / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutathione / analogs & derivatives
  • Glutathione / pharmacology
  • Kainic Acid / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Mutant Strains / metabolism*
  • Mutation / physiology
  • Nitric Oxide / metabolism*
  • Nitroarginine / pharmacology
  • Nitroso Compounds / pharmacology
  • Organ Culture Techniques
  • Oxyhemoglobins / pharmacology
  • Penicillamine / analogs & derivatives
  • Penicillamine / pharmacology
  • Platelet Aggregation Inhibitors / pharmacology
  • S-Nitroso-N-Acetylpenicillamine
  • S-Nitrosoglutathione

Substances

  • Antioxidants
  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Nitroso Compounds
  • Oxyhemoglobins
  • Platelet Aggregation Inhibitors
  • Nitroarginine
  • Biopterins
  • Nitric Oxide
  • S-Nitrosoglutathione
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • S-Nitroso-N-Acetylpenicillamine
  • sapropterin
  • Glutathione
  • Penicillamine
  • Cyclic GMP
  • Kainic Acid