Unique activities of cholecystokinin-58; physiological and pathological relevance

PURPOSE OF REVIEW: Cholecystokinin, a regulatory peptide found in multiple molecular forms in brain and small intestine, is responsible for integration of functions associated with the intake, digestion and absorption of food. Whether the different molecular forms have identical biological activities is controversial. New information suggests that CCK58, the largest form of cholecystokinin detected in blood and tissue, has unique functions compared with other forms, and may be the predominant, perhaps only, circulating form in mammals. RECENT FINDINGS: CCK58 has highly distinctive actions compared with shorter forms, most notably the strong stimulation of water secretion from the pancreas, and the lack of induction of pancreatitis by supramaximal doses of the peptide. Because CCK58 may be the main endogenous form of cholecystokinin, these recent findings have far reaching implications because almost all studies carried out with cholecystokinin have been done with shorter forms, predominately CCK8. Conclusions of studies using CCK8 or other shorter forms of cholecystokinin, therefore, may need to be reevaluated. SUMMARY: There is a compelling reason to reevaluate the role of cholecystokinin in health and disease because the predominant form of cholecystokinin, CCK58, has unique biological activities compared with forms of cholecystokinin used in previous basic and clinical studies.