Warfield A S, Segal S
Proc Natl Acad Sci U S A. 1978 Sep;75(9):4568-72. doi: 10.1073/pnas.75.9.4568.
The effects of experimental galactose toxicity on inositol and phosphatidylinositol (PtdIns) metabolism in synaptosomes from 0- to 30-day-old rats were investigated. Galactose toxicity was induced by feeding mothers a 40% galactose diet from the 12th day of pregnancy until 19 days postpartum when the offspring were weaned onto the maternal diet. There was no decrease in myoinositol concentrations and only a small decrease in PtdIns in synaptosomes from galactose-fed rats relative to glucose-fed controls. Synaptosomes from rats on the two diets converted equivalent amounts of [U-14C]glucose to inositol and PtdIns. Acetylcholine stimulated [2-3H]inositol incorporation into PtdIns while producing a net decrease in PtdIns concentration in synaptosomes from 22- to 30-day-old rats. However, the phospholipid response to acetylcholine in synaptosomes from galactose-fed rats was impaired. Thus, the acetylcholine-stimulated labeling of PtdIns was 40--50% lower in these synaptosomes while the effect on PtdIns concentration was reduced by a maximum of 55%. The data suggest that galactose-fed rats may have either a deficiency in the number of acetylcholine receptors or a defect in some step between receptor-neurotransmitter interaction and PtdIns breakdown.
研究了实验性半乳糖毒性对0至30日龄大鼠突触体中肌醇和磷脂酰肌醇(PtdIns)代谢的影响。通过在怀孕第12天至产后19天给母鼠喂食40%半乳糖饮食来诱导半乳糖毒性,此时将后代断奶并喂食母鼠的饮食。与喂食葡萄糖的对照组相比,喂食半乳糖的大鼠突触体中的肌醇浓度没有降低,PtdIns仅略有下降。两种饮食的大鼠的突触体将等量的[U-14C]葡萄糖转化为肌醇和PtdIns。乙酰胆碱刺激[2-3H]肌醇掺入PtdIns,同时导致22至30日龄大鼠突触体中PtdIns浓度净下降。然而,喂食半乳糖的大鼠突触体中对乙酰胆碱的磷脂反应受损。因此,这些突触体中乙酰胆碱刺激的PtdIns标记降低了40%-50%,而对PtdIns浓度的影响最多降低了55%。数据表明,喂食半乳糖的大鼠可能要么乙酰胆碱受体数量不足,要么在受体-神经递质相互作用和PtdIns分解之间的某个步骤存在缺陷。