Multiple forms and locations for the peripheral-type benzodiazepine receptor.

The pharmacological effects of benzodiazepines are mediated through a class of recognition sites associated with the neuronal gamma-aminobutyric acidA (GABAA) receptor. A second class of benzodiazepine binding sites is found in virtually all mammalian peripheral tissues, in blood cells, and in glial cells in the brain, but its functions remain unclear. Although these peripheral-type benzodiazepine binding sites (PBBS) have been localized to the mitochondrial outer membrane in many tissues, a growing body of evidence suggests that they may also exist on the plasma membrane. Plasma membrane PBBS have been described in heart, liver, adrenal, and testis and on hemopoietic cells. In rat liver, the two subcellular forms of PBBS are found separately in two different subpopulations of cells. The discovery of a plasma membrane fraction of PBBS clearly has implications for some of its putative functions, including steroidogenesis, mitochondrial respiration, heme metabolism, calcium channel modulation, cell growth, and immunomodulation. This commentary reviews the evidence for two locations for the PBBS and discusses the relevance of mitochondrial and plasma membrane forms with regard to structure, molecular biology, and proposed roles.