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  • Title: Biology of gut cholecystokinin and gastrin receptors.
    Author: Shulkes A, Baldwin GS.
    Journal: Clin Exp Pharmacol Physiol; 1997; 24(3-4):209-16. PubMed ID: 9131287.
    Abstract:
    1. The stomach hormone gastrin and the intestinal hormone cholecystokinin (CCK) share a common C-terminal pentapeptide sequence but have different biological roles. Gastrin is the major stimulant of gastric acid secretion and has a growth stimulatory effect on the secretory part of the stomach. The physiological roles of CCK are the stimulation of pancreatic secretion and the contraction of the gall-bladder. 2. Several classes of receptors have been defined for peptides of the gastrin/CCK family. The CCKA receptor on pancreatic acini has a greater affinity for sulfated CCK than for gastrin, while the gastrin/CCKB receptor in gastric mucosa and brain has similar affinities for both gastrin and CCK. Potent and selective antagonists have been developed for both receptor classes. 3. The structures of the CCKA and gastrin/CCKB receptors have been deduced from the nucleotide sequences of cloned cDNA. The receptors, which both belong to the family with seven transmembrane segments, control secretion via similar signalling mechanisms. Occupation of either receptor leads to activation of phospholipase C, with resultant increases in intracellular levels of inositol triphosphate and Ca2+. Mitogenic signalling pathways are also being defined. 4. Recent studies have questioned the previous assumption that gastrin precursors are inactive. Glycine-extended gastrin17 has been shown to stimulate mitogenesis in some cell lines and may also have an autocrine role in the growth of colonic cancers. The receptors involved, which are clearly distinct in binding properties from the CCKA and gastrin/CCKB receptors, have not yet been cloned. Specific antagonists for the novel receptors will be required to define their function in further detail.
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