Effect of chlorpromazine on isolated rat hepatocytes

Abstract

The effect of chlorprornazine hydrochloride (CPZ) (1–500 μM) on plasma membrane permeability and mitoehondrial respiratory function of isolated rat hepatocytes was studied. The endogenous oxygen consumption stimulated by 1 mM succinate was increased significantly by 5 μM CPZ, whereas the ability to exclude trypan blue (TB) was decreased significantly by 100 μM CPZ. The release of a cytosomal enzyme, lactate dehydrogenase (LDH), was increased significantly by 50 μM CPZ, whereas the release of glutamic-opalacetic transaminase (GOT) was increased significantly by 100 μM. The endogenous oxygen consumption was decreased significantly by 150 μM CPZ. The respiration control ratio by 2 μm 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 μM) first produced a significant change in plasma membrane permeability to low molecular substances such as succinate and then at higher concentrations (50–100 μM) 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 μM) than those which produced significant changes in plasma membrane permeability of hepatocytes.