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BRIEF REVIEW BIOLOGY OF GUT CHOLECYSTOKININ AND GASTRIN RECEPTORS
Author(s) -
Shulkes Arthur,
Baldwin Graham S.
Publication year - 1997
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1997.tb01809.x
Subject(s) - gastrin , cholecystokinin , receptor , biology , cholecystokinin receptor , medicine , endocrinology , g protein coupled receptor , g cell , secretion , biochemistry
SUMMARY 1. The stomach hormone gastrin and the intestinal hormone cholecystokinin (CCK) share a common C‐terminal pentapep‐tide 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/CCK B 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 CCK A and gastrin/CCK B 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 Ca 2+ . Mitogenic signalling pathways are also being defined. 4. Recent studies have questioned the previous assumption that gastrin precursors are inactive. Glycine‐extended gastrin 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 CCK A and gastrin/CCK B receptors, have not yet been cloned. Specific antagonists for the novel receptors will be required to define their function in further detail.