Cholecystokinin--gene structure, and molecular forms in tissue and blood.
The gene structure of human cholecystokinin (CCK) is known and the cDNA structures are known for pig and rat. However, the molecular forms of CCK produced, stored and released from neural or endocrine cells cannot be predicted from the known structures of preprocholecystokinin derived from cDNA. It is well recognized that gastrin and CCK share carboxyl-terminal homology and similar processing to form the biologic active peptides. Comparisons of the structures of preprogastrin and preprocholecystokinin reveal a similar degree of homology in the midregion of the precursors (the structure of preprogastrin 55-59 and preprocholecystokinin 39-42 is His-Arg-Arg-Gln-Leu). Gastrin-34 (whose amino terminus corresponds to position 58 of preprogastrin) is formed by cyclization of glutamine to pyrrolidone carboxylic acid subsequent to cleavage at the double basis site. Identical posttranslational processing in this region would yield CCK-61. However, CCK-58 is the largest biologically active peptide so far isolated and chemically characterized. CCK can be found in high concentrations in gut and brain but the molecular forms differ in the two tissues. Thus, the most abundant forms in the intestine are CCK-58, followed by CCK-39, CCK-33, and CCK-8, whereas in the brain CCK-8 is the most abundant form, followed by CCK-58 and CCK-5. The brain contains in contrast to the intestine little or no CCK-39 and CCK-33. Therefore differences in posttranslational processing between gut and brain are assumed. The predominant small CCK forms in the brain act presumably as neurotransmitters. Large and small molecular forms are released from the endocrine cell of the gut and act as circulating hormones. Several problems have hindered the characterization and quantitation of CCK forms in tissue and blood. The large forms (CCK-58, CCK-39, CCK-33) are easily lost because they are more basic and bind to glass and plastic surfaces. In addition to recovery problems, CCK-58 can be readily degraded into smaller forms at neutral or basic pH in tissue extracts and in blood or plasma. When special care is taken to prevent these problems, we have shown that, in the dog, CCK-58 is not only the most abundant molecular form in the intestinal mucosa but also in the circulating blood. The physiology and pathophysiology of circulating CCK (regulation of pancreatic secretion, of the motility of the gallbladder and the bowel, and involvement in satiety mechanisms) has to be studied further.
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002766:Cholecystokinin / Q000235:genetics*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D010455:Peptides / Q000235:genetics; D011487:Protein Conformation; D011498:Protein Precursors / Q000235:genetics
D010455:Peptides; D011498:Protein Precursors; C042082:preprocholecystokinin; D002766:Cholecystokinin