Chapter 111 - Endozepines

Abstract

The term endozepines is defined as endogenous ligands for benzodiazepine (BZD) receptors that have specific binding sites. The search for endogenous ligands for BZD receptors has led to the discovery of diazepam-binding inhibitor (DBI), a 10-kDa peptide originally identified from the rat brain for its ability to displace diazepam from its binding sites. Endozepines have been originally characterized as inverse agonists of the central-type benzodiazepine receptor (CBR) that is an intrinsic part of the GABAA receptor-chloride channel complex. In the brain and in peripheral nervous tissues, endozepines are exclusively expressed by glial cells. The release of endozepines from cultured astrocytes is finely regulated by neurotransmitters and neuropeptides. Endozepines exert their effects either through classical central- and peripheraltype benzodiazepine receptors or through G-protein coupled receptors. Intracerebroventricular injection of endozepines causes marked effects on anxiety, sleep, and food consumption. The concentration of Endozepines in the brain and cerebrospinal fluid is affected in various diseases, including depression and hepatic encephalopathy.