Inhibition of choline incorporation into brain lipids in rats by urethane, a proposed mechanism of depression of the central nervous system.
Concentrations and specific radioactivities of choline, acetylcholine, phosphorylcholine, lipid choline, and sn-glycero-3-phosphorylcholine after i.v. injection of methyl-14C-choline were measured in the brain of untreated controls and of rats anesthesized with urethane. The specific activity was found to be decreased during deep anesthesia by 40% in acetylcholine, 20-30% in phosphorylcholine, 50-75% in lipid choline, and 30-40% in sn-glycero-3-phosphoryl-choline. No significant change was detected in the specific activity of choline. The brain concentration of acetylcholine was increased by 40%, the concentration of sn-glycero-3-phosphorylcholine, however, was diminished by 10% during anesthesia. No change was found in the concentration of the other choline containing compounds investigated. Measuring choline incorporation into 4 subcellular fractions of brain tissue specific activities were found to be decreased by the same percentage, although 2 fractions (nuclei and microsomes) were higher labelled than the 2 other fractions (crude mitochondria with synaptosomes and lysosomes). A correlation between the biochemical and the functional alterations is supported by the dose-effect relationships on both parameters. It is suggested that urethane reduces turnover of lipids and by that mechanism inhibits the exocytotic release of the transmitter from presynaptic nerve endings.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002794:Choline / Q000378:metabolism*; D002854:Chromatography, Paper; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006868:Hydrolysis; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D008297:Male; D051381:Rats; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014520:Urethane / Q000494:pharmacology*
D014520:Urethane; D002794:Choline