Benzodiazepine Receptor Agonists Modulate Thymocyte Apoptosis Through Reduction of the Mitochondrial Transmembrane Potential

• Published in: Japanese Journal of Pharmacology 1999, Vol.79(2), pp.177-183
• Main Authors: Yutaka, Tanimoto, Yoshiaki, Onishi, Yutaka, Sato, Harutoshi, Kizaki
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Benzodiazepine; Benzodiazepines - pharmacology; Benzodiazepinones - pharmacology; Binding Sites; Caspase Inhibitors; Cells, Cultured; Clonazepam - pharmacology; Dexamethasone - pharmacology; Diazepam - pharmacology; Drug Interactions; Drug Synergism; Etoposide - pharmacology; GABA-A Receptor Agonists; Male; Membrane Potentials - drug effects; Mice; Mice, Inbred BALB C; Mitochondria - drug effects; Mitochondrial permeability transition; Protease Inhibitors - pharmacology; Proteasome; Protein Biosynthesis; Proteins - drug effects; RNA, Messenger - metabolism; Thymocyte; Thymus Gland - cytology; Thymus Gland - drug effects
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1254/jjp.79.177

Peripheral-type benzodiazepines have been shown to exert immunological effects. In this study, we examined the effects of the peripheral-type benzodiazepines on murine thymocytes. Murine thymocytes that were incubated with the peripheral-type benzodiazepines underwent apoptosis associated with the collapse of mitochondrial transmembrane potential (Δφm). The drugs stimulated dexamethasone- and etoposide-induced apoptosis with the enhanced collapse of Δφm. The central-type benzodiazepines had no effect on either the Δφm or apoptosis. The reduction of Δφm depended on protein synthesis and protein phosphorylation. These results suggest that the immunomodulating effect of benzodiazepines is in part due to the modulation of thymocyte apoptosis associated with the collapse of Δφm.