We measured several biochemical effects of 10 days of intragastric administration of phosphatidylcholine (10 mmoles/kg) to rats because of the expanding clinical use of chronic phosphatidylcholine treatment for disorders involving impaired cholinergic neurotransmission. The plasma and erythrocyte choline concentrations were increased 3.5-fold, which was the same percent increase as found after an acute treatment with phosphatidylcholine. The lipid and fatty acid compositions of the plasma were also altered; free and total cholesterol levels increased, triglycerides increased, the monoene fatty acids generally decreased, and the diene and tetraene fatty acids generally increased. We found no effect of this treatment on the hepatic microsomal cytochrome P-450 activity or on the N-demethylation of benzphetamine or methamphetamine. Ten days of phosphatidylcholine treatment increased the concentration of choline in the brain but had no effect on the concentration of acetylcholine, the activity of choline acetyltransferase, cholinesterase activity, the apparent KD or Bmax of muscarinic receptors, or the fatty acid composition of rat brain lipids. These findings indicate that the largest effect caused by this treatment was an increase in the choline levels. No indication of altered cholinergic metabolism was observed. Further studies of the effects of chronic phosphatidylcholine treatment are required to clarify its therapeutic mechanism of action.
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