In this paper the possible roles of cholecystokinin (CCK), gastrin, or gastrin-related peptides and their receptors in human gastrointestinal diseases are reviewed. For CCK/CCK A receptors (CCK A -R), the evidence for their proposed involvement in diseases caused by impaired CCK release or CCK A -R mutations, pancreatic disorders (acute/chronic pancreatitis), gastrointestinal motility disorders (gallbladder disease, irritable bowel syndrome), pancreatic tumor growth and satiety disorders, is briefly reviewed. The evidence that has established the involvement of gastrin/CCK B -R in mediating the action of hypergastrinaemic disorders, mediating hypergastrinaemic effects on the gastric mucosa (ECL hyperplasia, carcinoids, parietal cell mass), and acid-peptic diseases, is reviewed. The evidence for their possible involvement in mediating growth of gastric and pancreatic tumours and possible involvement of gastrin-related peptides in colon cancers, is reviewed briefly.Since the discovery of cholecystokinin (CCK) in 1928 by Ivy & Oldberg of its action on the gallbladder and structural characterization by Mutt & Jorpes (1968), similar to the closely-related peptide, gastrin, whose acid-releasing activity was described in 1905 by Edkins and structural characterization by Gregory & Tracy in 1964, there have been many studies to attempt to define their roles in both physiological and pathological gastrointestinal processes (Jorpes & Mutt 1973;Lamers et al. 1990; Liddle 1994;Walsh 1994;Baldwin 1995;Guo & Townsend, Jr. 2000;Otsuki 2000;Dockray et al. 2001) . Despite recent insights elucidating the structure of the two G-protein-coupled receptors that mediate their cellular actions (i.e., the CCK A and CCK B receptor) (Wank 1995), characterization of receptor location, peptide and receptor genes, development of receptor antagonists and receptor and peptide knockout animals (Liddle 1994;Jensen 1994;Walsh 1994;Langhans et al. 1997; Hinkle & Samuelson 1999;Lacourse et al. 1999;Miyasaka et al. 1999;deTullio et al. 2000), especially the role of CCK and to a lesser extent, gastrin, in normal gastrointestinal physiology as well as in clinically important gastrointestinal pathologic states, remains largely unclear and in many cases, controversial. In this review the latter aspect will be primarily dealt with, which is their role in clinically important processes rather than their role in normal physiology. By this it is meant their role in disease states which cause clinical symptoms in man.In this review these disorders will be divided into those involving primarily CCK A and those involving primarily CCK B receptors. Because only sulfated CCK analogues have a high affinity for CCK A Liddle 1994), CCK A -R disorders involve the potential role of CCK in disease states. Gastrin and CCK can interact with CCK B receptors Liddle 1994); however, much more information is available on the role of gastrin causing CCK B receptor-mediated disorders than CCK.
Clinically important gastrointestinal disorders involving CCK or CCK A r...
