CCK-B receptor: Chemistry, molecular biology, biochemistry and pharmacology

Cholecystokinin (CCK) is a peptide originally discovered in the gastrointes tinal tract but also found in high density in the mammalian brain. The C-te rminal sulphated octapeptide fragment of cholecystokinin (CCK8) constitutes one of the major neuropeptides in the brain; CCK8 has been shown to be inv olved in numerous physiological functions such as feeding behavior, central respiratory control and cardiovascular tonus, vigilance states, memory pro cesses, nociception, emotional and motivational responses. CCK8 interacts with nanomolar affinities with two different receptors desig nated 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 u se to study the anatomy of CCK pathways, the neurochemical and pharmacologi cal properties of this peptide and the clinical perspectives offered by man ipulation of the CCK system will be reported. The physiological and patholo gical implication of CCK-B receptor will be confirmed in CCK-B receptor def icient mice obtained by gene targeting (Nagata et al,, 1996. Proc. Natl. Ac ad. Sci. USA 93, 11825-11830). Moreover, CCK receptor gene structure, delet ion and mutagenesis experiments, and signal transduction mechanisms will be discussed. (C) 1999 Elsevier Science Ltd. All rights reserved.