Two subcellular locations for peripheral‐type benzodiazepine acceptors in rat liver

Abstract

Subcellular fractionation of rat liver by differential centrifugation showed the mitochondrial fractions to have the greatest enrichment of ‘peripheral‐type’ benzodiazepine acceptor. Two peaks of acceptor sites were found on isopycnic density‐gradient centrifugation, one peak (ϱ= 1.19 g/ml) corresponding to the peak of mitochondria as judged by marker enzyme distribution and by transmission electron microscopy, and the other peak (ϱ= 1.17 g/ml) which is not mitochondrial as judged by the lack of mitochondrial enzyme markers. Whereas the density of the mitochondrial acceptor was sensitive to sonication and was shown to have an outer‐membrane location, the density of the non‐mitochondrial acceptor was insensitive to sonication. The non‐mitochondrial acceptor was shown not to be associated with Golgi, lysosomes, rough endoplasmic reticular microsomes, peroxisomes, or some type of plasma membranes, as jugged by differences in the distribution of marker activities. No enrichment of benzodiazepine acceptor was found in the purified nuclear fraction. Both acceptors were shown to be peripheral‐type high‐affinity acceptors as judged by ligand specificities and by photoaffinity labelling.

Tissue-Specific Regulation of the Peripheral Benzodiazepine Receptor by Antidepressants and Lithium

“…The hepatic PBR are localized on the outer membrane of the mitochondria as well as in nonmitochondrial subcellular sites, such as the Golgi apparatus, lysosomes, rough endoplasmic reticular microsomes, peroxisomes or plasma membrane [37]. It is possible that the changes observed in hepatic PBR binding are an adaptive mechanism to altered mitochondrial energy metabolism due to the stimulatory effect of the tested drugs on biogenic amines.…”

The Cytotoxicity of Tumor Necrosis Factor Depends on Induction of the Mitochondrial Permeability Transition

“…The PBzR is associated with the outer mitochondrial membrane (31)(32)(33), and the PBzR agonist PK11195 (34,35) potentiates induction of the MPT in isolated mitochondria as well as in intact hepatocytes (36). Table II details the killing of L929 fibroblasts treated with TNF in the presence of PK11195, FGIN 1-27 (37), or chlorodiazepam (38).…”

Isolation of the mitochondrial benzodiazepine receptor: association with the voltage-dependent anion channel and the adenine nucleotide carrier.

“…Bz and isoquinolines with high affinity for the peripheral receptors influence numerous physiological processes, including cholesterol transfer in the adrenal gland associated with mitochondrial adrenal steroid synthesis (11)(12)(13) and mitochondrial respiration (14,15). The peripheral receptor, localized to mitochondria by subcellular fractionation (16,17), is also designated the mitochondrial Bz receptor (mBzR).…”