Cholecystokinin—From Local Gut Hormone to Ubiquitous Messenger

Abstract

Cholecystokinin (CCK) was discovered in 1928 in jejunal extracts as a gallbladder contraction factor. It was later shown to be member of a peptide family, which are all ligands for the CCK1 and CCK2 receptors. CCK peptides are known to be synthetized in small intestinal endocrine I-cells and cerebral neurons. But in addition, CCK is expressed in several endocrine glands (pituitary cells, thyroid C-cells, pancreatic islets, the adrenals, and the testes); in peripheral nerves; in cortical and medullary kidney cells; in cardial myocytes; and in cells of the immune system. CCK peptides stimulate pancreatic enzyme secretion and growth, gallbladder contraction, and gut motility, satiety and inhibit acid secretion from the stomach. Moreover, they are major neurotransmitters in the brain and the periphery. CCK peptides also stimulate calcitonin, insulin, and glucagon secretion, and they may act as natriuretic peptides in the kidneys. CCK peptides are derived from proCCK with a C-terminal bioactive YMGWMDFamide sequence, in which the Y-residue is partly O-sulfated. The plasma forms are CCK-58, -33, -22, and -8, whereas the small CCK-8 and -5 are potent neurotransmitters. Over the last decades, CCK expression has also been encountered in tumors (neuroendocrine tumors, cerebral astrocytomas, gliomas, acoustic neuromas, and specific pediatric tumors). Recently, a metastastic islet cell tumor was found to cause a specific CCKoma syndrome, suggesting that circulating CCK may be a useful tumor marker.

A conserved neuropeptide system links head and body motor circuits to enable adaptive behavior

“…Brain CCK has been increasingly implicated as a key regulator in diverse aspects of behavior, including feeding, satiety, memory, nociception and anxiety. 14,44,[55][56][57][58] Thus our studies elucidating mechanisms for NLP-12 regulation of circuit function in the compact nematode nervous system may have important and broadly applicable implications for neuromodulation in more complex systems.…”

Cholecystokinin Expression in the Development of Postinfarction Heart Failure

“…Cholecystokinin (CCK) is another appetite-regulated hormone that is widely distributed throughout various organs and tissues [8-10] and exists in various molecular forms (CCK-58, CCK-33, CCK-22, CCK-8, and CCK-4) [11]. However, the variation in bioactive CCKs is small in among species.…”

“…The multifunctionality of CCK suggests that it may have potential as a target in the evaluation and treatment of various diseases [18-20]. A recent study demonstrated that CCK was expressed at high concentrations in cardiac myocytes [21] despite being synthesized predominantly in the gastrointestinal tract and central nervous system [10]. These findings indicate that CCK has a variety of effects as a novel cardiovascular hormone.…”

Genomic signatures of extreme body size divergence in baboons

“…The CCKR signaling pathway coordinates food intake by controlling visceral functions and behavior Woods 2005). Cholecystokinin (CCK) stimulates the secretion of pancreatic digestive enzymes, the production and excretion of bile into the intestine, the delay of gastric emptying, and the inhibition of food intake Rehfeld 2017). Through its role as a satiety signal and regulator of energy intake, CCK is thought to act as a regulator of body weight Woods 2005).…”