Peripheral Benzodiazepine Receptors in Health and Disease

Two main types of benzodiazepine receptors have been identified: central type, which is found in the brain mainly in the cortex, limbic areas and cerebellum, and peripheral type, which is found in the kidneys, lungs, ovaries, testes, adrenal glands and blood cells, but is also present in the CNS, in particular in glial cells. Peripheral benzodiazepine receptors (PBR) are detected in most of the animals including insects, mollusks, pisces, amphibians, aves, mammals, and as well in various plants and bacteria. PBR are involved in apoptosis, proliferation, porphyrin transport, immunomodulation, and many other processes, such as steroidogenesis in adrenal glands, brain, male and female gonads, biological adaptation to stress, etc. Subcellularly, PBR are predominantly localized on the outer mitochondrial membrane and are part of a complex that consists of three components: 18 kDa receptor protein, 32 kDa voltage-dependent anion channel and 30 kDa adenine nucleotide carrier. Only 18 kDa receptor protein was assigned as PBR. In steroid synthesizing tissues, PBR control cholesterol import from the outer to the inner mitochondrial membranes and is vital for steroid biosynthesis. PBR in plants as Arabidopsis are also involved in steroid transport in mitochondria. In normal brain, PBR are localised in mitochondria of glial cells and expressed in very low concentrations. Their expression rises after microglial activation following brain injury and inflammation. Changes in the level of PBR have been observed in neurological and psychiatric disorders including multiple sclerosis, Alzheimer’s, Parkinson’s and Huntington’s diseases. Stress affects PBR bidirectionally: acute stress is associated with increased PBR density, whereas chronic stress down-regulates PBR. The PBR ligands control cell proliferation and differentiation, and several cancers including breast, colon, ovary, liver have been associated with increased PBR number. In aged animals and humans PBR in adrenals, kidneys, testes, lymphocytes, and brain are differentially changed probably due to malfunctioning of PBR.