Peripheral-type benzodiazepine receptors: Their implication in brain disease

Abstract

Benzodiazepines are well known for their therapeutic properties, which include anxiolytic, anticonvulsant, muscle-relaxant, and hypnotic effects. Central-type benzodiazepine receptors (CBRs), which are considered to mediate these effects, are present exclusively in the central nervous system (CNS), where they are located on the outer cell membranes of neurons. Peripheral-type benzodiazepine receptors (PBRs) are present in peripheral tissues and also in glia cells of the CNS. Although CBRs are located primarily on the cell membranes of neurons, PBRs are particularly abundant on the membranes of mitochondria. CBR are coupled to γ-aminobutyric acid A (GABAA) receptors, but PBRs are not. PBRs are constituted of at least three protein subunits of different molecular weights, i.e., 18-kDa, 32-kDa, and 30-kDa protein subunits. PBRs have been implicated in various functions, including steroidogenesis, mitochondrial respiration, cell growth and differentiation, and responses to stress. The presence of PBRs in glia of the CNS suggests that they may be involved in glial functions in the brain. This review discusses the involvement of glial PBRs in various neurological diseases, such as degenerative brain diseases, neurotoxic insults, brain damage, brain cancer, and anxiety disorders. It is suggested that the involvement of PBRs in steroidogenesis appears to play an important role in neuroprotection. It is also suggested that PBRs may play a role in glial uptake of excitatory amino acids and their clearance from the brain, and herewith execute neuroprotective capabilities. With this review, we hope to clarify the potential of PBRs as targets for treatment of neurological disorders and prevention of brain damage. Drug Dev. Res. 50:355–370, 2000. © 2000 Wiley-Liss, Inc.