Role of sulfate ester in influencing biologic activity of cholecystokinin-related peptides.
In dispersed acini from guinea pig, mouse, or rat pancreas cholecystokinin-(27-33) is a full agonist, and removing the sulfate ester from the tyrosine residue in position 27 caused a 100- to 300-fold decrease in potency with no change in efficacy. In dispersed acini from mouse or rat pancreas, cholecystokinin-(27-32)-NH2 is a partial agonist, and removing the sulfate ester from the tyrosine in position 27 abolished the efficacy. The desulfated peptide was able, however, to interact with CCK receptors with a potency that was threefold less than that of cholecystokinin-(27-32)-NH2 and therefore functioned as a cholecystokinin receptor antagonist. In dispersed acini from guinea pig pancreas cholecystokinin-(27-32)-NH2 is a cholecystokinin receptor antagonist. Removing the sulfate ester from the tyrosine residue in position 27 of cholecystokinin(27-32)-NH2 caused a fourfold decrease in potency but did not abolish the ability of the peptide to interact with cholecystokinin receptors; therefore, desulfated cholecystokinin-(27-32)-NH2 functioned as a cholecystokinin receptor antagonist.
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002264:Carboxylic Acids; D002766:Cholecystokinin / Q000378:metabolism / Q000494:pharmacology / Q000031:analogs & derivatives; D004952:Esters; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000378:metabolism; D012844:Sincalide / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013431:Sulfates
D002264:Carboxylic Acids; D004952:Esters; D010446:Peptide Fragments; D011949:Receptors, Cholecystokinin; D013431:Sulfates; C025997:cholecystokinin (27-33); C044201:cholecystokinin (26-33); C038242:cholecystokinin (27-32)-amide; D002766:Cholecystokinin; D000681:Amylases; D012844:Sincalide