Cholecystokinin: Clinical aspects of the new biology

Cholecystokinin (CCK) is a classic gut hormone that has been known for almost a century to regulate gallbladder emptying, pancreatic enzyme secretion, and gastrointestinal motor activity. In 1968, the CCK structure was identified by Viktor Mutt and Erik Jorpes from porcine gut extracts as a peptide of 33 amino acid residues. Based on that structure, physiological, immunochemical, molecular, and cell biological research has since expanded the insight into the biology of CCK remarkably. Thus, CCK was the first identified intestinal satiety signal to the brain. Moreover, the CCK gene is now known to be expressed in different molecular forms not only in the gut, but very much so in central and peripheral neurons, in addition to extra-intestinal endocrine cells, immune cells, cardiomyocytes, spermatogenic cells, and certain fat cells. Accordingly, CCK peptides function not only as hormones. They are also neurotransmitters, paracrine growth and satiation factors, anti-inflammatory cytokines, incretins, adipokins, myokines, potential fertility factors, and tumor markers. Consequently, CCK biology has now opened windows for insights into pathophysiology with diagnostic and therapeutic possibilities in metabolic disorders (obesity, eating disorders, and diabetes mellitus), gallbladder disease, neuropsychiatric diseases (cerebral tumors, memory, and anxiety disorders), cardiac diseases (prognosis in heart failure), neuroendocrine and pediatric tumors, as well as perhaps infertility.