The biology of cholecystokinin and gastrin peptides.
Cholecystokinin (CCK) and gastrin together constitute a family of homologous peptide hormones, which are both physiological ligands for the gastrin/CCK-B receptor, whereas the CCK-A receptor binds only sulfated CCK-peptides. CCK peptides are mainly produced in small intestinal endocrine I-cells and in cerebral neurons. CCK peptides regulate pancreatic enzyme secretion and growth, gallbladder contraction, intestinal motility, satiety and inhibit gastric acid secretion. Moreover, they are potent neurotransmitters in the brain and the periphery. CCK peptides are derived from proCCK and have the bioactive heptasequence -Tyr(SO4)-Met-Gly-Trp-Met-Asp-Phe-NH2 as their C-terminus. The dominant forms in plasma are CCK-58, CCK-33, CCK-22 and CCK-8, whereas CCK-8 is the major transmitterform. Due to scarcity of specific assays, knowledge about CCK in disease is still limited. Gastrin peptides are mainly synthetized in antroduodenal G-cells, from where they are released to blood to regulate gastric acid secretion and mucosal growth. Small amounts are synthetized further down the intestinal tract, in the foetal pancreas, in a few cerebral and peripheral neurons, in the pituitary gland and in spermatozoes. Gastrin peptides are derived from progastrin and all have the C-terminal bioactive hexasequence -Tyr (SO4)-Gly-Trp-Met-Asp-Phe-NH2. The major gastrin forms in tissue and plasma are gastrin-34 and gastrin-17, but also gastrin-71, -14 and -6 have been identified. Gastrin peptides are secreted in excessive amounts from gastrinomas and are expressed at lower levels in bronchogenic, colorectal, gastric, ovarian and pancreatic cancers. A carcinogenetic significance of gastrin peptides remains, however, to be proven.
Rehfeld
Jens F
JF
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. jens.f.rehfeld@rh.regionh.dk
Friis-Hansen
Lennart
L
Goetze
Jens P
JP
Hansen
Thomas V O
TV
D000818:Animals; D049109:Cell Proliferation; D002766:Cholecystokinin / Q000737:chemistry* / Q000378:metabolism*; D005755:Gastrins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D009092:Mucous Membrane / Q000166:cytology / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D043887:Receptor, Cholecystokinin B / Q000378:metabolism
D005755:Gastrins; D043887:Receptor, Cholecystokinin B; D002766:Cholecystokinin