| Candidate ID: | R1170 |
| Source ID: | DB08862 |
| Source Type: | approved; investigational |
| Compound Type: |
small molecule
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| Compound Name: |
Cholecystokinin
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| Synonyms: |
CCK-PZ; Human CCK-33; Human cholecystokinin-33; Pancreozymin
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| Molecular Formula: |
--
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| SMILES: |
--
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| DrugBank Description: |
Cholecystokinin ( also known as _CCK or CCK-PZ_) is a peptide hormone of the gastrointestinal system which is responsible for stimulating the digestion of fat and protein. Cholecystokinin, previously called _pancreozymin_, is synthesized and secreted by enteroendocrine cells in the duodenum (the first portion of the small intestine) and leads to the release of bile and digestive enzymes. CCK also acts as an appetite suppressant and has been studied for weight management regimens .
Normally, it is an endogenous hormone but is available commercially for diagnostic processes and replacement in pancreatic insufficiency . in the octapeptide form.
Cholecystokinin is one of the first gastrointestinal hormones discovered, identified more than 90 years ago due to its ability to stimulate gallbladder contraction in 1928. Soon after, it was recognized to be identical to the factor responsible for stimulating pancreatic exocrine secretion in 1943 . This hormone has also been shown to have positive effects on enteric smooth muscle contraction and on nerve activity at multiple locations in the peripheral and central nervous system. In addition to its roles in promoting smooth muscle cell contraction/exocrine cell secretion, CCK promotes cell growth, energy production, gene expression and protein synthesis, processes that have profound for drug development . This drug has also been investigated for possible antipsychotic properties, owing to its effect on CCK receptors in the brain .
Recent studies have suggested that cholecystokinin also plays a major role in inducing drug tolerance to opioids such as morphine and heroin, and is partially implicated in experiences of pain hypersensitivity during opioid withdrawal .
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| CAS Number: |
9011-97-6
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| Molecular Weight: |
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| DrugBank Indication: |
For use as a diagnostic aid for evaluation of gallbladder disorders. It is also used in conjunction with secretin in pancreatic insufficiency .
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| DrugBank Pharmacology: |
Cholecystokinin (CCK) plays an imperative role in facilitating digestion within the small intestine. The activation of the CCK1 receptor by CCK has demonstrated to be responsible for a wide variety of important physiologic functions, including the stimulation of gallbladder, contraction and exocrine pancreatic enzyme secretion, delay of gastric emptying, relaxation of the sphincter of Oddi, inhibition of gastric acid secretion, and induction of satiety . Cholecystokinin is also produced by neurons in the enteric nervous system and is found to be widely distributed in the brain . An interesting function of CCK is the role it plays in stimulating the CCK receptor and subsequently regulating food consumption, which may prove to be a highly useful treatment for obesity . Exogenous administration CCK has been widely studied .
Diseases resulting from excessive or deficient secretion of cholecystokinin are rare. Cholecystokinin deficiency has been described in humans as part of autoimmune polyglandular syndrome, characterized as a malabsorption syndrome clinically similar to pancreatic exocrine insufficiency. Additionally, there is increasing evidence that alterations in expression of cholecystokinin or its receptor within the brain may possibly play a role in the pathogenesis of various types of anxiety disorders and schizophrenia .
Foodstuffs flowing into the small intestine are mostly made up of large macromolecules (proteins, polysaccharides, and triglyceride) that require digestion into small molecules (amino acids, monosaccharides, fatty acids) in order to be absorbed. Digestive enzymes from the pancreas and bile salts from the liver (which are stored in the gallbladder) are necessary for digestion. Cholecystokinin is the primary stimulus for the release of pancreatic enzymes and bile secretion into the small intestine. Additionally, cholecystokinin, induces contraction of the gallbladder muscle, resulting in the reduction of gallbladder size and evacuation of bile .
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| DrugBank MoA: |
Cholecystokinin (CCK) is a peptide hormone discovered in the small intestine. Together with secretin and gastrin, CCK constitutes the classical gut hormone triad. In addition to gallbladder contraction, CCK also regulates pancreatic enzyme secretion and growth, intestinal motility, satiety signaling and the inhibition of gastric acid secretion. CCK is, however, also a transmitter in central and intestinal neurons. Notably, CCK is the most ubiquitously found neuropeptide in the human brain. Owing to difficulties in developing accurate assays for the hormone, knowledge about CCK secretion in disease is limited. Available data indicate, however, that proCCK is expressed in certain malignant neuroendocrine tumors and sarcomas, whereas the secretion of CCK is affected in celiac disease and the eating disorder bulimia nervosa. Stimulation with exogenous CCK has proved this protein useful in diagnostic imaging of gallbladder and pancreatic diseases, as well as testing of medullary thyroid carcinomas .
Cholecystokinin, a natural polypeptide which is formed in the amine precursor uptake and decarboxylation (APUD) cells of the proximal mucosa of the small intestine, promotes contraction of the gallbladder muscle, resulting in the reduction of gallbladder size and the expression of bile . Cholecystokinin stimulates secretion of pancreatic digestive enzymes and secretion from the glands of Brunner .
CCK is composed of a five amino acid sequence at the carboxyl terminus that is identical to that of gastrin. The carboxyl terminus confers the biologic activity of CCK; as a result, gastrin has CCK-mimicking activity and CCK has gastrin-mimicking activity. The amino acid sequence similarity has made the creation of assays for CCK cumbersome, due to the fact that antibodies specific for the biologically active portion the molecule often cross-react with gastrin. This hormone circulates in the blood at concentrations 10 to 100 times greater than that of CCK .
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| Targets: |
Cholecystokinin receptor type A agonist; RAF proto-oncogene serine/threonine-protein kinase agonist; Mitogen-activated protein kinase 3; Pro-epidermal growth factor; Protein kinase C beta type agonist; Gastrin/cholecystokinin type B receptor agonist
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| Inclusion Criteria: |
Therapeutic strategy associated
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