Fewer metabolites of dietary choline reach the blood of rats after treatment with lithium.
Choline is an important precursor for the biosynthesis of acetylcholine, phosphatidylcholine and sphingomyelin. It is also a major source of labile methyl groups. Lithium is an important component of the treatment of bipolar affective illness, and it inhibits choline transport across membranes. We studied the effect of lithium treatment upon the appearance in blood, liver and intestine of metabolites formed from dietary choline. Rats were treated for 9 days with 2 mEq/kg lithium carbonate or water. Animals were fasted overnight, and on the 10th day were fed with a solution containing radiolabeled choline chloride. The lithium-treated groups also received 2.0 mEq/kg lithium as part of this solution. After an oral dose of 1 ml of a 1 mM choline solution, the lithium-treated animals had significantly lower levels of choline-derived radiolabel in blood than did controls at 30, 60, 120, and 180 minutes (47% (+/- 5%; SEM), 51% (+/- 7%), 59% (+/- 4%) and 74% (+/- 9%), respectively). We observed similar decreases of the accumulation in blood, at 180 minutes after the dose, of choline-derived radiolabel when choline was administered at lower or higher concentrations. After an oral treatment containing 0.1, 1 or 10 mM choline, lithium treated animals accumulated 69% (+/- 6%; SEM), 66% (+/- 11%) and 72% (+/- 7%) as much radiolabel in serum as did controls. Most of the radiolabel found in blood at 180 minutes was in metabolites of choline which are formed within liver (betaine and phosphatidylcholine). The diminished accumulation of radiolabel in serum after lithium treatment was not due to increased accumulation of label by erythrocytes, liver or gut wall. We suggest that lithium influences the release by liver of betaine and phosphatidylcholine.
Pomfret
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EA
Department of Pathology, Boston University School of Medicine, MA 02118.
O'Connor
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Zola
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Zeisel
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SH
D000818:Animals; D001622:Betaine / Q000097:blood; D001692:Biological Transport / Q000187:drug effects; D002794:Choline / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D010713:Phosphatidylcholines / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains
D010713:Phosphatidylcholines; D001622:Betaine; D008094:Lithium; D002794:Choline