Effect of chlorpromazine on isolated rat hepatocytes

The effect of chlorpromazine hydrochloride (CPZ) (1-500 microM) on plasma membrane permeability and mitochondrial respiratory function of isolated rat hepatocytes was studied. The endogenous oxygen consumption stimulated by 1 mM succinate was increased significantly by 5 microM CPZ, whereas the ability to exclude trypan blue (TB) was decreased significantly by 100 microM CPZ. The release of a cytosomal enzyme, lactate dehydrogenase (LDH), was increased significantly by 50 microM CPZ, whereas the release of glutamic-opalacetic transaminase (GOT) was increased significantly by 100 microM. The endogenous oxygen consumption was decreased significantly by 150 microM CPZ. The respiration control ratio by 2 microM carbonylcyanide-m-chlorphenyl hydrazon (CCP) showed significant decreases at all concentrations of CPZ studied; and this might be attributable to the suppression by CPZ of the respiratory stimulation induced by CCP. The results indicated that CPZ at a low concentration (5 microM) first produced a significant change in plasma membrane permeability to low molecular substances such as succinate and then at higher concentrations (50-100 microM) produced significant release of the cytosomal and mitochondrial enzymes, LDH and GOT. They also indicated that the concentrations of CPZ which produced significant effects on respiratory function were higher (above 150 microM) than those which produced significant changes in plasma membrane permeability of hepatocytes.