Impairment of the nitric oxide/cyclic GMP pathway in cerebellar slices prepared from the hph-1 mouse.
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.
Department of Neurochemistry, Institute of Neurology, London, UK.
M P
MP
Brand
A
A
Briddon
J M
JM
Land
J B
JB
Clark
S J
SJ
Heales
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001708:Biopterins / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains / Q000378:metabolism*; D009154:Mutation / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D009924:Organ Culture Techniques; D010108:Oxyhemoglobins / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D026422:S-Nitrosoglutathione
D000975:Antioxidants; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D009603:Nitroso Compounds; D010108:Oxyhemoglobins; D010975:Platelet Aggregation Inhibitors; D019335:Nitroarginine; D001708:Biopterins; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D026423:S-Nitroso-N-Acetylpenicillamine; C003402:sapropterin; D005978:Glutathione; D010396:Penicillamine; D006152:Cyclic GMP; D007608:Kainic Acid