Molecular cellular and behavioral aspects of peripheral-type benzodiazepine receptors.

Peripheral-type benzodiazepine receptors (PBR) are prominent in peripheral organs, whereas in the brain, they are sparse and located mainly in glial cells. The PBR bind with high affinity the ligands Ro 5-4864 (4'-chlorodiazepam) and PK 11195 (an isoquinoline carboxamide derivative), but not clonazepam, which binds with high affinity to central-type benzodiazepine receptors (CBR). Subcellularly, PBR are predominantly localized on the outer mitochondrial membrane. It appears that the PBR are composed of three subunits: an 18-kDa subunit that binds isoquinoline carboxamide derivatives; a 30-kDa subunit that binds benzodiazepines; and a 32-kDa subunit labeled by the benzodiazepine [3H]AHN 086, the voltage-dependent anion channel. Recently, complementary DNA (cDNA) encoding for rat and human PBR was isolated and sequenced. The PBR gene is located in the q13.3 region of the long arm of human chromosome 22. The PBR play a major role in steroidogenesis, controlling cholesterol mitochondrial transport. Diazepam-binding inhibitor and its processing products, as well as porphyrins, have been suggested as putative endogenous ligands for these receptors. The PBR ligands have been shown to control cell proliferation and differentiation, and the binding capacity for these ligands is enhanced in some malignant tumors. Stress has been demonstrated to affect PBR bidirectionally. Acute stress is associated with increased PBR density, whereas chronic stress down-regulates PBR.