Endozepines and their receptors: Structure, functions and pathophysiological significance

Publication date: Available online 5 July 2019Source: Pharmacology & TherapeuticsAuthor(s): Marie-Christine Tonon, Hubert Vaudry, Julien Chuquet, Florent Guillebaud, Jinjiang Fan, Olfa Masmoudi-Kouki, David Vaudry, Damien Lanfray, Fabrice Morin, Vincent Prevot, Vassilios Papadopoulos, Jean-Denis Troadec, Jérôme LeprinceAbstractThe existence of specific binding sites for benzodiazepines (BZs) in the brain has prompted the search for endogenous BZ receptor ligands designated by the generic term « endozepines ». This has led to the identification of an 86-amino acid polypeptide capable of displacing [3H]diazepam binding to brain membranes, thus called diazepam-binding inhibitor (DBI). It was subsequently found that the sequence of DBI is identical to that of a lipid carrier protein termed acyl-CoA-binding protein (ACBP). The primary structure of DBI/ACBP has been well preserved, suggesting that endozepines exert vital functions. The DBI/ACBP gene is expressed by astroglial cells in the central nervous system, and by various cell types in peripheral organs. Endoproteolytic cleavage of DBI/ACBP generates several bioactive peptides including a triakontatetraneuropeptide that acts as a selective ligand of peripheral BZ receptors/translocator protein (PBR/TSPO), and an octadecaneuropeptide that activates a G protein-coupled receptor and behaves as an allosteric modulator of the GABAAR. Although DBI/ACBP is devoid of a signal peptide, endozepines are released by astrocytes in a re...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research