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Evidence that CCK-58 has structure that influences its biological activity.

Publication ,  Journal Article
Reeve, JR; Eysselein, VE; Rosenquist, G; Zeeh, J; Regner, U; Ho, FJ; Chew, P; Davis, MT; Lee, TD; Shively, JE; Brazer, SR; Liddle, RA
Published in: Am J Physiol
May 1996

Many biologically active peptides exist in multiple molecular forms, but the functional significance of regions outside the region of bioactivity is unknown. The biological and immunological data presented in this study indicate that cholecystokinin-58 (CCK-58), unlike other forms of cholecystokinin, has structure that influences its bioactivity. CCK-58 was purified from acid extracts of canine intestinal mucosa until a single absorbance peak was obtained during reverse-phase chromatography. Amino acid analysis precisely determined the peptide concentrations of purified CCK-58 and synthetic CCK-8. Our hypothesis was that if the amino terminus of CCK-58 influences its bioactivity then its activity would be modified when this region was removed from the peptide. To evaluate the importance of the amino terminus of CCK-58 to influence its biological activity, the abilities of CCK-58 and CCK-8 to release amylase from pancreatic acini were compared before and after tryptic digestion. Tryptic digestion of CCK-58 decreased the half-maximal stimulation (EC50) for amylase release from 96 to 28 pM. The EC50 for digested CCK-58 was similar to that for CCK-8 (17 pM). These results suggest that CCK-58 has a structure that shields its bioactive carboxyl terminus. This is further supported by the finding that carboxyl fragments generated from CCK-58 by trypsin or by partial acid hydrolysis were greater than twofold more immunoreactive than the intact CCK-58. The diminished activity of CCK-58 SK shields the carboxyl terminus, which is important to its biological and immunological activities.

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Published In

Am J Physiol

DOI

ISSN

0002-9513

Publication Date

May 1996

Volume

270

Issue

5 Pt 1

Start / End Page

G860 / G868

Location

United States

Related Subject Headings

  • Trypsin
  • Structure-Activity Relationship
  • Spectrum Analysis
  • Peptide Fragments
  • Pancreas
  • Molecular Sequence Data
  • In Vitro Techniques
  • Hydrolysis
  • Drug Storage
  • Dogs
 

Citation

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Reeve, J. R., Eysselein, V. E., Rosenquist, G., Zeeh, J., Regner, U., Ho, F. J., … Liddle, R. A. (1996). Evidence that CCK-58 has structure that influences its biological activity. Am J Physiol, 270(5 Pt 1), G860–G868. https://doi.org/10.1152/ajpgi.1996.270.5.G860
Reeve, J. R., V. E. Eysselein, G. Rosenquist, J. Zeeh, U. Regner, F. J. Ho, P. Chew, et al. “Evidence that CCK-58 has structure that influences its biological activity.Am J Physiol 270, no. 5 Pt 1 (May 1996): G860–68. https://doi.org/10.1152/ajpgi.1996.270.5.G860.
Reeve JR, Eysselein VE, Rosenquist G, Zeeh J, Regner U, Ho FJ, et al. Evidence that CCK-58 has structure that influences its biological activity. Am J Physiol. 1996 May;270(5 Pt 1):G860–8.
Reeve, J. R., et al. “Evidence that CCK-58 has structure that influences its biological activity.Am J Physiol, vol. 270, no. 5 Pt 1, May 1996, pp. G860–68. Pubmed, doi:10.1152/ajpgi.1996.270.5.G860.
Reeve JR, Eysselein VE, Rosenquist G, Zeeh J, Regner U, Ho FJ, Chew P, Davis MT, Lee TD, Shively JE, Brazer SR, Liddle RA. Evidence that CCK-58 has structure that influences its biological activity. Am J Physiol. 1996 May;270(5 Pt 1):G860–G868.

Published In

Am J Physiol

DOI

ISSN

0002-9513

Publication Date

May 1996

Volume

270

Issue

5 Pt 1

Start / End Page

G860 / G868

Location

United States

Related Subject Headings

  • Trypsin
  • Structure-Activity Relationship
  • Spectrum Analysis
  • Peptide Fragments
  • Pancreas
  • Molecular Sequence Data
  • In Vitro Techniques
  • Hydrolysis
  • Drug Storage
  • Dogs