Benzodiazepine receptor agonists modulate thymocyte apoptosis through reduction of the mitochondrial transmembrane potential

Peripheral-type benzodiazepines have been shown to exert immunological effe cts. In this study, we examined the effects of the peripheral-type benzodia zepines on murine thymocytes. Murine thymocytes that were incubated with th e peripheral-type benzodiazepines underwent apoptosis associated with the c ollapse of mitochondrial transmembrane potential (Delta psi(m). The drugs s timulated dexamethasone- and etoposide-induced apoptosis with the enhanced collapse of Delta psi(m). The central-type benzodiazepines had no effect on either the Delta psi(m) or apoptosis. The reduction of Delta psi(m) depend ed on protein synthesis and protein phosphorylation. These results suggest that the immunomodulating effect of benzodiazepines is in part due to the m odulation of thymocyte apoptosis associated with the collapse of Delta psi( m).