Sequence variation outside the "active" region of dog and rabbit cholecystokinin-58 results in bioactivity differences.

Published

Journal Article

OBJECTIVES: We propose that regions outside the bioactive 7-amino acid carboxyl terminus of cholecystokinin (CCK)-58 influence its biological activity. Here we evaluate if sequence variation of the N-terminal regions of rabbit and canine CCK-58 changes their biological activities. METHODS: Cholecystokinin-like immunoreactivity was purified from rabbit intestinal extracts by reverse phase and ion-exchange high-performance liquid chromatography steps. The peptide was characterized by microsequence and mass spectral characterizations of the intact and tryptic peptides. Canine and rabbit CCK-58 were evaluated for their CCK1 and CCK2 receptor binding, receptor activation, and immunologic properties. RESULTS: The sequence of rabbit CCK-58 differs from that of canine CCK-58 in 9 of the amino terminal 40 residues. Canine CCK-58 was approximately 3-fold more potent than rabbit CCK-58 for CCK1 receptor binding and CCK2 receptor binding, but about the same potency for stimulation of amylase release from purified acinar cells. The canine peptide was 9-fold more immunoreactive than rabbit CCK-58. CONCLUSIONS: Canine and rabbit CCK-58 have different biological and immunologic properties that can only result from differences in their N-terminal sequences which influence the properties of their identical carboxyl termini. These results are the first direct demonstration that amino acids outside the C-terminus of CCK-58 influence CCK biological activity.

Full Text

Duke Authors

Cited Authors

  • Reeve, JR; Liddle, RA; Shively, JE; Lee, TD; Keire, DA; Chew, P; Vigna, SR

Published Date

  • April 2006

Published In

Volume / Issue

  • 32 / 3

Start / End Page

  • 306 - 313

PubMed ID

  • 16628087

Pubmed Central ID

  • 16628087

Electronic International Standard Serial Number (EISSN)

  • 1536-4828

Digital Object Identifier (DOI)

  • 10.1097/01.mpa.0000218315.04954.77

Language

  • eng

Conference Location

  • United States