Editorial [Hot Topic:Cholecystokinin Receptors as Targets in Medicinal Chemistry (Guest Editor: Daniel Fourmy)]

Cholecystokinin (CCK) and gastrin are among the first gastrointestinal hormones discovered. Since the first sequencing of these regulatory peptides in 1964 and 1968, a huge amount of basic and translational research work has been carried. Due to their wide tissue distribution in both the central nervous system and peripheral organs and to the number of biological processes which they regulate, CCK and gastrin receptors are undoubtedly important candidate targets in medicine. These receptors are still the subject of intensive research today. In this special issue of Current Topics in Medicinal Chemistry are gathered 10 articles related to cholecystokinin and gastrin receptors written by world-wide acknowledged experts in the field. In a first article, Jens Rehfeld and colleagues draw a picture of the available knowledge related to cellular synthesis, secretion and processing of cholecystokinin and gastrin peptides as well as to major physiological effects of the two peptides. In a second article Larry Miller and collegues describe the biochemical and cell biological mechanisms of cholecystokinin receptor regulation. These include receptor phosphorylation/dephosphorylation by specific enzymes, internalization/ intracellular trafficking and oligomerisation. In a third article, Florence Noble reports major data on the design of peptidic ligands specific for the CCK receptors and some pharmacological properties of these ligands, with a special focusing on the central nervous system. In the following two articles, Rosario Herranz and Barrett Kalindjian and colleagues review the last five literature years of medicinal chemistry of non peptide ligands of CCK1R and CCK2R. In a sixth article, Kyoko Miyasaka and colleagues describe available data on CCK1R polymorphism and its pathophysiological relevance in humans. In a seventh article, Marc Berna and Robert Jensen report in detail the established and possible roles of CCK1 and CCK2 receptors in gastrointestinal and metabolic diseases and discuss available results from human agonist/antagonist studies. In the following paper, Graham Baldwin reviews the most recent data in relation to CCK receptors and cancer and possible therapeutic implications, which has been a field of intensive investigations. In another article, Jean-Claude Reubi focuses his report on expression of CCK receptors in certain neuroendocrine tumours and on the promising use of CCK-related radiolabelled ligands to identify and cure these cancers. In the last article, Irina Tikhinova and colleagues, introduce and develop the concept of target-structure based design of ligands which could be applied to CCK receptors on the basis of data from CCK receptor binding site studies and further to other G-protein coupled receptors for which no satisfactory ligand is available. I wish to express my thanks to all contributors of this special issue which hopefully will be an helpful source of information for investigators in this field as well as in the wide field of G protein coupled receptors.