Bachmann C, Colombo J P
Pediatr Res. 1984 Apr;18(4):372-5. doi: 10.1203/00006450-198404000-00014.
Sparse-fur mice, 28 d of age with the x-chromosomal inherited defect of ornithine carbamoyltransferase, were used to investigate if tryptophan and the serotonin pathway in the brain are affected in this animal model which closely resembles the human inborn error of metabolism. Increased concentrations of tryptophan and 5-hydroxyindole acetic acid were found in forebrain and brainstem. Application of probenecid, which blocks the efflux of 5-hydroxyindole acetic acid from the brain, led to an augmented accumulation of this serotonin metabolite in the affected males. We conclude that the increased concentration of tryptophan in brain and the subsequent increased flux through the serotonin pathway are a consequence of hyperammonemia in this inherited defect of urea synthesis. Surprisingly, increased carbamoylphosphate synthetase was found in the liver of the male sparse-fur mice.
采用具有X染色体遗传性鸟氨酸氨甲酰基转移酶缺陷、28日龄的稀毛小鼠，来研究色氨酸和大脑中的血清素途径在这种与人类先天性代谢缺陷极为相似的动物模型中是否受到影响。在前脑和脑干中发现色氨酸和5-羟吲哚乙酸的浓度升高。应用丙磺舒（它可阻断5-羟吲哚乙酸从大脑中流出）会导致这种血清素代谢物在受影响的雄性小鼠体内积累增加。我们得出结论，在这种尿素合成的遗传性缺陷中，大脑中色氨酸浓度的升高以及随后通过血清素途径的通量增加是高氨血症的结果。令人惊讶的是，在雄性稀毛小鼠的肝脏中发现氨甲酰磷酸合成酶增加。
