DBI (diazepam binding inhibitor): the precursor of a family of endogenous modulators of GABAA receptor function. History, perspectives, and clinical implications

Biochemical, electrophysiological, and lately, molecular biological techniques have shown that GABAA receptors are heterogeneous supramolecular complexes and can be divided into at least three major subgroups: GABAA1, GABAA2, and GABAA3. They differ mainly in the structural and functional properties of the allosteric modulatory center associated with each one of them. This paper will review the present state of research based on the evidence that DBI (diazepam binding inhibitor) and its natural processing products can selectively modulate GABAergic transmission at different GABAA receptor subtypes. Furthermore, the possibility that the DBI family of peptides represents a novel and meaningful neurochemical correlate for neuropsychiatric pathology, sustained by an alteration of GABAergic transmission, will be discussed.