title: N-terminal fragments of CCK-(26-33) as cholecystokinin receptor antagonists in guinea pig pancreatic acini.
abstract: In the present study we synthesized different N-terminal fragments and analogues of the C-terminal octapeptide of cholecystokinin [CCK-(26-33)] and examined their actions on dispersed acini prepared from guinea pig pancreas. None of the N-terminal fragments or analogues altered basal amylase release. Analogues of CCK-(26-32), CCK-(26-31), and CCK-(26-30) inhibited CCK-(26-33)-stimulated amylase, and there was a close correlation between the ability of an analogue to inhibit stimulated amylase and the analogue's ability to inhibit binding of 125I-cholecystokinin. N-acetyl-CCK-(26-29)-amide at concentrations as high as 100 microM did not inhibit CCK-(26-33)-stimulated amylase release or binding of 125I-CCK. For those analogues that antagonized CCK-(26-33)-stimulated amylase release the antagonism was of the competitive type and was specific for those secretagogues that interact with the cholecystokinin receptor. Removing the C-terminal amide from N-acetyl-CCK-(26-31)-amide caused a 10-fold decrease in the inhibitory potency, whereas removing the C-terminal amide from N-acetyl-CCK-(26-30)-amide did not alter the inhibitory potency of the peptide. Removing the sulfate ester from the tyrosine residue in position 27 of N-acetyl-CCK-(26-31) did not alter the inhibitory potency of the peptide, whereas removing the sulfate ester from the tyrosine residue in position 27 of N-acetyl-(26-30) caused a three- to fivefold decrease in the inhibitory potency of the peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.forename: J D
authors.initials: JD
authors.lastname: Gardner
authors.forename: M
authors.initials: M
authors.lastname: Knight
authors.forename: V E
authors.initials: VE
authors.lastname: Sutliff
authors.forename: R T
authors.initials: RT
authors.lastname: Jensen
mesh_terms: D000681:Amylases / Q000378:metabolism; D000818:Animals; D002766:Cholecystokinin / Q000378:metabolism; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011949:Receptors, Cholecystokinin; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D011956:Receptors, Cell Surface; D011949:Receptors, Cholecystokinin; C044201:cholecystokinin (26-33); D002766:Cholecystokinin; D000681:Amylases; D012844:Sincalide