Inhibition of L-methionine uptake and incorporation by chlorpromazine in preimplantation mouse embryos.
These studies indicate that chlorpromazine causes a rapid inhibition of the uptake and incorporation of L-[Me-3H]methionine in preimplantation mouse embryos in vitro. Concentrations of chlorpromazine from 10-5 M to 10-4 M inhibit L-[Me-3H]methionine uptake and incorporation in late four-cell embryos in 15 min. Concentrations of chlorpromazine from 2 times 10-5 M to 10-4 M inhibit uptake and incorporation in early blastocysts in 15 min to comparable degrees, suggesting that the effect of chlorpromazine on the early blastocyst is primarily on methionine transport, and not on protein synthesis. Lineweaver-Burk plots constructed from 15-min uptake values of methionine in the presence of various concentrations of chlorpromazine indicate that 5 times 10-5 M-chlorpromazine competitively inhibits methionine uptake in blastocysts, while 10-4 M-chlorpromazine non-competitively inhibits transport. Efflux experiments support the idea that chlorpromazine acts as an inhibitor of the active methionine influx processes, and not through acceleration of efflux. It is suggested that chlorpromazine may produce delayed implantation by directly affecting the preimplantation embryo, as well as through its known inhibitory effects on the hormonal functions of the maternal organism.
D000818:Animals; D001755:Blastocyst / Q000187:drug effects / Q000378:metabolism; D002746:Chlorpromazine / Q000494:pharmacology*; D003470:Culture Media; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006064:Gonadotropins, Equine / Q000494:pharmacology; D008715:Methionine / Q000378:metabolism*; D051379:Mice; D010060:Ovulation / Q000187:drug effects; D011247:Pregnancy; D014316:Tritium
D003470:Culture Media; D006064:Gonadotropins, Equine; D014316:Tritium; D008715:Methionine; D002746:Chlorpromazine