Cholecystokinin-27-32-amide. A member of a new class of cholecystokinin receptor antagonists.
In dispersed acini from guinea pig pancreas, cholecystokinin-27-32-amide (CCK-27-32-NH2) did not alter amylase secretion but was able to antagonize the stimulation caused by cholecystokinin-related agonists. CCK-27-32-NH2 caused a parallel rightward shift in the dose-response curve for the stimulation of amylase secretion caused by cholecystokinin and inhibited binding of 125I-labeled cholecystokinin to pancreatic acini. These results indicate that CCK-27-32-NH2 is a fully competitive cholecystokinin receptor antagonist. CCK-27-32-NH2 did not alter the rate of dissociation of bound 125I-cholecystokinin from pancreatic acini but was able to reverse the residual stimulation of enzyme secretion caused by first incubating pancreatic acini with a relatively high concentration of cholecystokinin. Compared to other cholecystokinin receptor antagonists, CCK-27-32-NH2 is the most potent antagonist described to date, i.e. 30 times more potent than N2,O2-dibutyryl guanosine 3':5'-monophosphate. These results also indicate that the COOH-terminal phenylalanine residue of cholecystokinin is essential for intrinsic cholecystokinin-like activity but is not essential for binding of the peptide to cholecystokinin receptors in pancreatic acini.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002766:Cholecystokinin / Q000378:metabolism* / Q000494:pharmacology* / Q000031:analogs & derivatives; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011949:Receptors, Cholecystokinin; D013329:Structure-Activity Relationship
D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D011949:Receptors, Cholecystokinin; D003994:Bucladesine; C038242:cholecystokinin (27-32)-amide; D002766:Cholecystokinin