Mechanism of action of cholecystokinin: a not atypical brain-gut peptide.
Brain-gut peptide action has been best studied in certain target cells of the gastrointestinal tract such as isolated pancreatic acini. Cholecystokinin (CCK) activation of pancreatic digestive enzyme secretion is initiated by specific receptors present in the basolateral membrane of the acinar cell. These receptors are highly selective for CCK and readily discriminate it from the homologous peptide, gastrin. Studies covalently crosslinking 125I-CCK to its receptor have revealed a binding glycoprotein subunit of Mr = 76,000 attached by a disulfide bridge to a Mr = 40,000 nonbinding subunit. Receptor occupancy leads to phosphotidylinositide breakdown and Ca2+ mobilization. Recent studies with the fluorescent chelate probe Quin-2 have shown that CCK increases cytosolic Ca2+ from a basal level of 100 nM to 500 approximately 1000 nM. The effects of Ca2+, and diacylglycerol produced by the breakdown of phosphoinositides, are believed mediated by activation of a group of protein kinases and phosphatases. CCK in the brain is present in neurons and is released from nerve endings by depolarization. The cellular mechanism of action of CCK, however, is essentially unknown. CCK application excites certain neurons but attempts to demonstrate effects on ion fluxes, phospholipid metabolism and protein phosphorylation have been negative to date. A possible explanations is provided by the finding that the brain CCK receptor shows differences in binding specificity from peripheral CCK receptors. Moreover, crosslinking studies reveal a single binding protein of Mr = 51,000. Thus, CCK may act differently in the brain and pancreas.
Williams
J A
JA
D000818:Animals; D001921:Brain / Q000502:physiology*; D001923:Brain Chemistry; D002118:Calcium / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002766:Cholecystokinin / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology; D010179:Pancreas / Q000201:enzymology / Q000502:physiology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000032:analysis; D011949:Receptors, Cholecystokinin
D011956:Receptors, Cell Surface; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; D000242:Cyclic AMP; D002118:Calcium