PERIPHERAL BENZODIAZEPINE RECEPTOR LIGANDS IN RAT-LIVER MITOCHONDRIA - EFFECT ON CHOLESTEROL TRANSLOCATION

Peripheral benzodiazepine receptors mediate cholesterol translocation between the outer and inner mitochondrial membranes in steroidogenic t issues. They are found in many other tissues too, including liver. We studied the effect of the peripheral benzodiazepine receptor ligands P K11195 hyl-N-(1-methylpropyl)isoquinoline-3-carboxamide], Ro 5-4864 (4 -chlorodiazepam), hemin, protoporphyrin IX and N-methyl protoporphyrin IX on cholesterol mitochondrial intermembrane transport of cholestero l in vitro in rat liver. Endogenous cholesterol translocation from out er to inner mitochondrial membranes was significantly increased by PK1 1195 and N-methyl protoporphyrin IX (140% and 150% increase, respectiv ely, at 1 mu M, P < 0.01). 5 mu M protoporphyrin IX, 1 mu M Ro 5-4864 and 5 mu M hemin was ineffective. When mitochondria were labeled with exogenous [4-C-14]cholesterol, PK11195 and N-methyl protoporphyrin IX were the most effective in increasing total cholesterol incorporation and cholesterol translocation into inner membranes, and their effect w as dose-dependent. These data suggest that in liver the binding to per ipheral benzodiazepine receptors is related to cholesterol translocati on and the interaction of ligands with these receptors may play a role in the complex mechanism of regulation of cholesterol traffic between liver mitochondrial membranes.