CCK-B receptor: chemistry, molecular biology, biochemistry and pharmacology.
Cholecystokinin (CCK) is a peptide originally discovered in the gastrointestinal tract but also found in high density in the mammalian brain. The C-terminal sulphated octapeptide fragment of cholecystokinin (CCK8) constitutes one of the major neuropeptides in the brain; CCK8 has been shown to be involved in numerous physiological functions such as feeding behavior, central respiratory control and cardiovascular tonus, vigilance states, memory processes, nociception, emotional and motivational responses. CCK8 interacts with nanomolar affinities with two different receptors designated CCK-A and CCK-B. The functional role of CCK and its binding sites in the brain and periphery has been investigated thanks to the development of potent and selective CCK receptor antagonists and agonists. In this review, the strategies followed to design these probes, and their use to study the anatomy of CCK pathways, the neurochemical and pharmacological properties of this peptide and the clinical perspectives offered by manipulation of the CCK system will be reported. The physiological and pathological implication of CCK-B receptor will be confirmed in CCK-B receptor deficient mice obtained by gene targeting (Nagata el al., 1996. Proc. Natl. Acad. Sci. USA 93, 11825-11830). Moreover, CCK receptor gene structure, deletion and mutagenesis experiments, and signal transduction mechanisms will be discussed.
Noble
F
F
Département de Pharmacochimie Moléculaire et Structurale, INSERM U266-CNRS UMR 8600, Université René Descartes, UFR des Sciences Pharmaceutiques et Biologiques, Paris, France.
Roques
B P
BP
D000818:Animals; D001923:Brain Chemistry / Q000235:genetics*; D002766:Cholecystokinin / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000737:chemistry* / Q000235:genetics*
D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin