The importance of the amino acid in position 32 of cholecystokinin in determining its interaction with cholecystokinin receptors on pancreatic acini

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Abstract

In the C-terminal heptapeptide of cholecystokinin, replacement of the penultimate residue, aspartic acid, by β-alanine caused a 300-fold decrease in potency with which the peptide stimulated enzyme secretion, whereas replacement by glutamic acid caused a 1000-fold decrease in potency. The β-alanine-substituted peptide was approximately ten times more potent when the N terminus was blocked with t-butyloxycarbonyl than when it was blocked with benzyloxycarbonyl, and the glutamic acid-substituted peptide was approximately twice as potent when the N terminus was blocked with t-butyloxycarbonyl than when it was blocked with benzyloxycarbonyl. Changes in the ability of the peptide to stimulate amylase secretion were acompanied by corresponding changes in the ability of the peptide to inhibit binding of 125I-labeled cholecystokinin. The magnitude of stimulation of enzyme secretion caused by a maximally effective peptide concentration was the same with each analogue as it was with the unaltered peptide. Rpelacing the aspartyl by β-alanine or glutamic acid or replacing of N-terminal t-butyloxycarbonyl moiety by benzyloxycarbonyl caused an equivalent decrease in the ability of the peptide to stimulate enzyme secretion and its ability to cause residual stimulation of enzyme secretion. In contrast, the N-terminal desamino analogue of cholecystokinin heptapeptide was ten times less potent than the unaltered peptide in stimulating amylase secretion, but 100 times less potent that the unaltered peptide in causing residual stimulation of enzyme secretion.

References (18)

  • T.-M. Lin et al.

    Gastroenterology

    (1976)
  • T.-M. Lin et al.

    Gastroenterology

    (1977)
  • B.W. Long et al.

    Gastroenterology

    (1977)
  • J.D. Gardner et al.

    Biochim. Biophys. Acta

    (1980)
  • M. Ceska et al.

    Clin. Chim. Acta

    (1969)
  • M. Ceska et al.

    Clin. Chim. Acta

    (1969)
  • J.S. Morley
  • M. Ondetti et al.

    Am. J. Dig. Dis.

    (1970)
  • J.D. Gradner et al.

    J. Clin. Invest.

    (1975)
There are more references available in the full text version of this article.

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Present address: Division of Gastroenetrology, Department of Medicine, Capital Hospital, Beijing, China.

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