Effect of cycloheximide on tryptophan binding to rat hepatic nuclei.
This study evaluated whether cycloheximide, an inhibitor of protein synthesis, would affect the binding of L-tryptophan to rat hepatic nuclei or nuclear envelopes. Previous reports have indicated that the binding of L-tryptophan to hepatic nuclear envelope protein was saturable, stereospecific, and of high affinity. Also, the administration of L-tryptophan rapidly stimulated hepatic protein synthesis. In this study, we determined that the addition of cycloheximide in vitro inhibited 3H-tryptophan binding to hepatic nuclei or nuclear envelopes. Heat-treated cycloheximide failed to have this inhibitory binding effect. In vivo treatment of rats with cycloheximide diminished in vitro 3H-tryptophan binding to hepatic nuclei of treated rats compared to controls. Puromycin, another inhibitor of hepatic protein synthesis, when added in vitro did not affect 3H-tryptophan binding to hepatic nuclei but did diminish in vitro binding after in vivo treatment. Thus, cycloheximide added in vitro diminished 3H-tryptophan binding to hepatic nuclei probably by its structural effect on the receptor while cycloheximide administered in vivo may also act in part by inhibiting protein synthesis.
Sidransky
H
H
Department of Pathology, George Washington University Medical Center, Washington, District of Columbia 20037, USA.
Verney
E
E
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007930:Leucine / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011691:Puromycin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014364:Tryptophan / Q000378:metabolism*; D014867:Water / Q000494:pharmacology
D000596:Amino Acids; D011500:Protein Synthesis Inhibitors; D014867:Water; D011691:Puromycin; D014364:Tryptophan; D003513:Cycloheximide; D007930:Leucine