Members of CRF Family and their Receptors: From Past to Future

G.      Liapakis; M.      Venihaki; A.      Margioris; D.      Grigoriadis; K.      Gkountelias

Abstract

Corticotropin releasing factor (CRF), originally isolated from the mammalian hypothalamus, is a 41 amino acid peptide that plays an important physiological role and is implicated in the pathophysiology of various diseases. In addition to CRF and its related peptides, a large number of small non-peptide CRF analogs have been recently synthesized, some currently in clinical trials having considerable therapeutic potential in the treatment of CRF-related illnesses. CRF and its related peptides exert their multiple actions by interacting with two types of plasma membrane G-protein coupled CRF receptors, the type 1 (CRF1) and type 2 (CRF2). These receptors, like all GPCRs consist of an amino-terminal extracellular region, a carboxyl-terminal intracellular tail and seven, membrane-spanning segments, connected by alternating intracellular and extracellular loops. This review describes the functional role of CRF receptors and their ligands emphasizing the structural elements that are important for their function and could potentially contribute in the development of future target-based approaches to design new CRF-related drugs which will enrich the pharmaceutical armoire against serious diseases.

Keywords: Binding, CRF-peptides, CRF-receptors, non-peptide antagonists, structure, physiological/pathophysiological role, signaling, Corticotropin releasing factor, 41 amino acid peptide, pathophysiology