Mechanism of trimethylamine-induced inhibition of macromolecular synthesis by mouse embryos in culture.
The effects of trimethylamine (TMA) on uptake mechanisms and lysosomal function were studied in mouse embryos, isolated yolk sacs and limb buds. TMA at 0.75 mM did not inhibit uptake of [14C]sucrose by yolk sacs of day 9 embryos or by day 15 isolated yolk sacs but did inhibit uptake of 125I-labelled bovine serum albumin ([125I]BSA) by day 15 isolated yolk sacs. Concentrations of TMA up to 2.5 mM did not inhibit lysosomal degradation of [125I]BSA by isolated yolk sacs, as judged by the release of trichloroacetic acid (TCA)-soluble radioactivity into the culture media. The inhibition of [125I]BSA uptake induced by TMA was reversible on removal of TMA. When day 8 embryos were cultured in serum containing [3H]leucine-labelled proteins, uptake and incorporation of radioactivity in 0.75 mM TMA-treated embryos was 47 and 44%, respectively, of that in untreated controls. TMA at 0.75 mM did not inhibit the uptake and incorporation of free [3H]leucine into embryonic protein nor the amount of free [3H]leucine taken up or incorporated into protein by day 12 isolated limb buds. It is concluded that the reduced macromolecular synthesis in embryos exposed to TMA is due to an inhibition of receptor-mediated uptake of nutrients by the yolk sac.
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Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
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D000818:Animals; D001769:Blood; D046508:Culture Techniques; D004622:Embryo, Mammalian / Q000187:drug effects / Q000378:metabolism*; D005121:Extremities / Q000196:embryology; D005260:Female; D007328:Insulin / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D007930:Leucine / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D008744:Methylamines / Q000494:pharmacology*; D051379:Mice; D014176:Protein Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013395:Sucrose / Q000378:metabolism; D014801:Vitamin A / Q000494:pharmacology; D015017:Yolk Sac / Q000187:drug effects / Q000378:metabolism
D007328:Insulin; D007976:Leupeptins; D008744:Methylamines; D014801:Vitamin A; D012710:Serum Albumin, Bovine; D013395:Sucrose; D007335:Insulin-Like Growth Factor II; D007930:Leucine; C032854:leupeptin; C023336:trimethylamine