title: Differences in receptor binding and stability to enzymatic digestion between CCK-8 and CCK-58.
abstract: OBJECTIVE
  It has been proposed that distinct tertiary structures of the C-terminus of CCK-8 and CCK-58 result in differences in stimulation of pancreatic amylase secretion. Binding of CCK-8 and CCK-58 to CCK-A and CCK-B receptors and stability to enzymatic digestion were used as independent probes for tertiary structure of the C-terminus.
  
  
  METHODS
  Canine CCK-58 was purified from intestinal extracts and CCK-8 was purchased. Their amounts were determined by amino acid analysis. The effect of tertiary structure on receptor binding at CCK-A receptors and CCK-B receptors was evaluated using membrane preparations from mouse pancreas and brain. The influence of C-terminal tertiary structure on stability to enzymatic digestion was evaluated by reacting CCK-8 and CCK-58 with endopeptidase 24:11.
  
  
  RESULTS
  CCK-58 was three times more potent than CCK-8 for binding mouse pancreatic membrane CCK-A receptors and equipotent to CCK-8 for binding mouse brain CCK-B receptors. CCK-8 was readily digested by endopeptidase 24:11, whereas CCK-58 was not.
  
  
  CONCLUSIONS
  The results strongly support the hypothesis that differences in tertiary structure of the carboxyl terminus of CCK-8 and CCK-58 influence receptor binding and stability to enzymatic digestion.
authors.affiliation: CURE Digestive Diseases Research Center, VAGLAHS, Los Angeles, CA 90073, USA. jreeve@ucla.edu
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Reeve
authors.forename: Douglas C
authors.initials: DC
authors.lastname: McVey
authors.forename: Nigel W
authors.initials: NW
authors.lastname: Bunnett
authors.forename: Travis E
authors.initials: TE
authors.lastname: Solomon
authors.forename: David A
authors.initials: DA
authors.lastname: Keire
authors.forename: F J
authors.initials: FJ
authors.lastname: Ho
authors.forename: Michael T
authors.initials: MT
authors.lastname: Davis
authors.forename: Terry D
authors.initials: TD
authors.lastname: Lee
authors.forename: John E
authors.initials: JE
authors.lastname: Shively
authors.forename: Steven R
authors.initials: SR
authors.lastname: Vigna
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002766:Cholecystokinin / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D004285:Dogs; D013058:Mass Spectrometry; D051379:Mice; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000378:metabolism; D017434:Protein Structure, Tertiary; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D012844:Sincalide / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C038823:cholecystokinin 58; D002766:Cholecystokinin; D015260:Neprilysin; D012844:Sincalide