Stimulation of the brain NO/cyclic GMP pathway by peripheral administration of tetrahydrobiopterin in the hph-1 mouse.

摘要: Mutations in GTP-cyclohydrolase I (GTP-CH) have been identified as causing a range of inborn errors metabolism, including dopa-responsive dystonia. GTP-CH catalyses the first step biosynthesis tetrahydrobiopterin (BH4), cofactor necessary for synthesis catecholamines and serotonin. Current therapy based on monoamine neurotransmitter replacement may be only partially successful correcting neurological deficits. The reason might that BH4 is also nitric oxide synthase. Using strain mutant GTP-CH-deficient (hph-1) mice, we demonstrate addition to impaired deficiency associated with diminished brain (as evaluated by measuring levels cyclic GMP), when compared wild-type animals. We found decline age all animals, but no gender-related differences. strong association between GMP hph-1 mice not acute peripheral administration (100 micromol/kg s.c.) significantly elevated concentration subsequently cerebellum, peaks at 2 3 h, respectively. suggest should considered states therapy.