Cycloheximide blocks the fall of plasma and tissue tryptophan levels after tryptophan-free amino acid mixtures.
The hypothesis that incorporation of tryptophan (TRY) into proteins is the mechanism underlying the decrease in plasma and tissue TRY levels after a TRY-free amino acid mixture was investigated. Rats fasted 15 hours were pretreated with saline or with the protein synthesis inhibitor cycloheximide (CHEX) and treated with saline or a TRY-free amino acid mixture. In a first experiment, in saline pretreated rats the TRY-free mixture caused a decrease of 49% in total plasma TRY, of 64% in free plasma TRY, of 66% in brain TRY and of 42% in liver TRY. After 5 mg/kg of CHEX the same TRY-free diet caused a decrease of 5% in total plasma TRY, 14% in free plasma TRY, 18% in brain TRY and 9% in liver TRY. In a second experiment, the TRY-free diet caused a 43% decrease of total plasma TRY in saline pretreated animals and a decrease of 15%, 6% and 2% respectively after the pretreatment with 0.3, 1.0 and 5.0 mg/kg of CHEX. In brain TRY, the TRY-free diet caused a 62% decrease in saline pretreated rats and a decrease of 38%, 20% and 19% respectively after the pretreatment with 0.3, 1.0 and 5.0 mg/kg of CHEX. Since 5.0 mg/kg of CHEX almost completely block protein synthesis and since doses of CHEX from 0.3 to 5.0 mg/kg cause a dose-dependent inhibition of protein synthesis, our data support the hypothesis that protein synthesis is the mechanism through which TRY-free mixtures decrease TRY levels.
Moja
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EA
Chair of Psychobiology, Medical School, University of Modena, Italia.
Restani
P
P
Corsini
E
E
Stacchezzini
M C
MC
Assereto
R
R
Galli
C L
CL
D000596:Amino Acids / Q000008:administration & dosage*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D014364:Tryptophan / Q000097:blood / Q000378:metabolism*
D000596:Amino Acids; D011500:Protein Synthesis Inhibitors; D014364:Tryptophan; D003513:Cycloheximide