Effect of benzodiazepines on tryptophan binding to rat hepatic nuclei.
This study evaluates whether or not some of the benzodiazepines would influence the binding of L-tryptophan to rat hepatic nuclei or nuclear envelopes. Previous publications have indicated that binding of L-tryptophan to hepatic nuclear envelope proteins was saturable, stereospecific, and of high affinity. In this study, we investigated whether some of the benzodiazepines would influence L-tryptophan binding to rat hepatic nuclei or nuclear envelopes as assayed by in vitro L-(5-3H) tryptophan binding. Our results indicate that the addition of chlordiazepoxide, diazepam, prazepam, flurazepam, nordazepam, N-desalkylflurazepam, temazepam, oxazepam, lorazepam, or 4-chlorodiazepam has little influence on the L-(5-3H) tryptophan binding to hepatic nuclei in vitro. However, the addition of demoxepam, the N-desalkylated compound of chlordiazepoxide, caused marked competition with 3H-tryptophan binding to hepatic nuclei in vitro. When chlordiazepoxide (1 mg/100 g body weight) is administered intraperitoneally 20 min before killing, the isolated hepatic nuclei reveal decreased specific L-tryptophan binding compared to controls. Also, rats pretreated with chlordiazepoxide intraperitoneally before tube-feeding L-tryptophan revealed diminished tryptophan-induced hepatic nuclear RNA efflux and protein synthesis. Our results suggest that chlordiazepoxide, possibly by itself or through a metabolite, can act to affect hepatic nuclear binding of L-tryptophan and to inhibit the stimulatory effect of L-tryptophan on hepatic protein synthesis.
Sidransky
H
H
Department of Pathology, George Washington University Medical Center, Washington, D.C. 20037.
Verney
E
E
Cosgrove
J W
JW
Schwartz
A M
AM
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009685:Nuclear Envelope / Q000187:drug effects / Q000378:metabolism; D011132:Polyribosomes / Q000187:drug effects / Q000378:metabolism; D014176:Protein Biosynthesis; D012313:RNA / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014364:Tryptophan / Q000378:metabolism*
D001569:Benzodiazepines; D012313:RNA; D014364:Tryptophan