Myoinositol and phosphatidylinositol metabolism in synaptosomes from galactose-fed rats.

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Abstract
The effects of experimental galactose toxcity on inositol and phosphatidylinositol (PtdIns) metabolism in synaptosomes from 0-30 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 2 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 22-30 day old rats. The phospholipid response to acetylcholine in synaptosomes from galactose-fed rats was impaired. 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%. Galactose-fed rats may have a deficiency in the number of acetylcholine receptors or a defect in some step between receptor-neurotransmitter interaction and PtdIns breakdown. [These findings have relevance to the neurotoxic effects of human galactosemia].