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Effect of Benzodiazepines on Tryptophan Binding to Rat Hepatic Nuclei

Department of Pathology, The George Washington University Medical Center, Washington, D.C. 20037

Ethel Verney

Department of Pathology, The George Washington University Medical Center, Washington, D.C. 20037

James W. Cosgrove

Department of Pathology, The George Washington University Medical Center, Washington, D.C. 20037

Arnold M. Schwartz

Department of Pathology, The George Washington University Medical Center, Washington, D.C. 20037

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.

Key Words: Receptor binding • nuclear envelopes • protein synthesis

Toxicologic Pathology, Vol. 20, No. 3-1, 350-356 (1992)
DOI: 10.1177/019262339202000305


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