Cholecystokinin, production

Cholecystokinin Endocrine cells in mucosa of duodenum Breakdown products of lipid and, to a small extent, protein digestion in duodenum Inhibits gastric emptying and gastric secretion stimulates contraction of gallbladder stimulates secretion of digestive enzymes from pancreas... 

Most pancreatic secretion takes place during the intestinal phase. The intestinal hormone secretin stimulates release of a large volume of pancreatic juice with a high concentration of bicarbonate ion. Secretin is released in response to acidic chyme in the duodenum (maximal release at pH < 3.0). The intestinal hormone cholecystokinin is released in response to the presence of the products of protein and lipid digestion. Cholecystokinin then stimulates the release of digestive enzymes from the pancreas. 

Rehfeld JF Cholecystokinin expression in the central nervous system. Eur Neuropsychopharmacol 2(3) 189-191, 1992b Rehfeld JF The molecular nature of cholecystokinin in plasma—an in vivo immunosorption study in rabbits. Scand J Gastroenterol 29 110-121, 1994 Rehfeld JF, Hansen HF Characterization of preprocholecystokinin products in the porcine cerebral cortex evidence of different processing pathways. J Biol Chem 261 5832-5840, 1986... 

There are a variety of peptide hormones acting in the gut the gastrins stimulate gastric acid secretion secretin and somatostatin inhibit the production of gastrins. Cholecystokinin and somatostatin can inhibit gastric acid secretion directly, and the former one causes the gall-bladder to contract and thus force bile into the duodenum. 

Gastric acid production is regulated by both the autonomic nervous system and several hormones. The parasympathetic nervous system, via the vagus nerve and the hormone gastrin, stimulates the parietal cell to produce gastric acid, acting both directly on parietal cells and indirectly through the stimulation of the secretion of the hormone histamine from ECL cells. Vasoactive intestinal peptides, cholecystokinin and secretin all inhibit acid production. 

Bile, pH 7.8-8.6, is produced continuously in humans. Hepatic bile is concentrated and stored in the gall bladder between meals. It is ejected from the gall bladder and flows into the duodenum when food enters the intestine. The main constituents of bile are bile salts, bilirubin, end products of hemoglobin breakdown, the electrolytes sodium, chloride, and bicarbonate, cholesterol, phospholipids, and lecithin. The gall bladder contracts within 30 min after eating due to liberation of cholecystokinin. The most effective stimulus to this is food high in fat. 

Pentagastrin is a short peptide that stimulates the production of gastric acid from the stomach by a direct action on gastrin receptors and of calcitonin from thyroid C cells (1). It also acts on cholecystokinin receptors centrally and stimulates the release of adrenocorticotropin (ACTH) and hence the production of glucocorticoids (2). 

In response to a meal, cholecystokinin is released from the intestine and causes relaxation of the sphincter of Oddi and contraction of the gallbladder (see Chapter 48). This allows a concentrated solution of micelles (consisting of bile salts, lecithin, and cholesterol) to enter the intestine. In the intestinal lumen, dietary cholesterol and the products of triglyceride digestion (predominantly free fatty acids and monoglycerides) are incorporated into mixed micelles. Micelles deliver lipolytic products to the mucosal surface. To carry out these functions, a critical micellar bile acid concentration of 2ramoI/L is necessary. 

Calcitonin is secreted continuously under conditions of normocalcemia, and the synthesis of calcitonin is increased when the calcium concentrations in plasma and intracellular fluids increase. Hypermagnesemia has a similar effect on calcitonin production. In hypocalcemia, the production of calcitonin falls. The gastrointestinal hormones—gastrin, glucagon, cholecystokinin, and secretin—and high dietary calcium also stimulate calcitonin production. Long-term hypercalcemia may cause hyperplasia of the C cells. 

Phthalimidomethyl-substituted 477-pyrido[4,3-( ]-l-thia-2,4-diazine 1,1-dioxide derivative 125 undergoes hydrazino-lysis to produce the (7-3-aminomethyl-substituted product, which is then acylated to yield the amido adducts 126 (R = H, Ph R =Ar, NHAr) as potential cholecystokinin/gastric receptor ligands (Equation 17) <1997BSB781>. Similar acylation chemistry has been applied to the synthesis of related 5-(methylamides) of 2/7-benzo-l-thia-2,4-diazine 1,1-dioxides (see Section 9.05.9.1.3) <2001CHE237>. 

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