Cholecystokinin-octapeptide fragments: binding to brain cholecystokinin receptors

Eur J Pharmacol. 1984 Oct 1;105(1-2):49-55. doi: 10.1016/0014-2999(84)90647-2.


Structural determinants of cholecystokinin octapeptide (CCK-8) binding to central nervous system receptors have been studied to assess the relative importance of the amino and the carboxyl end of the active peptide sequence, CCK-(26-33). The relative ability to inhibit equilibrium binding of [125I]CCK-33 to guinea pig cortical membranes was determined for a series of amino and carboxyl terminal fragments of CCK-8. While N-acetyl CCK-(26-29), N-acetyl CCK-(26-30) amide and N-acetyl CCK-(26-31) amide were inactive, the N-acetyl CCK-(26-32) amide fragment displayed binding to central receptors. Of the carboxyl terminal peptide fragments, both CCK-(29-33) and CCK-(30-33) bound less potently than CCK-8; CCK-(31-33) interacted more weakly than the tetra- and pentapeptide, but with a higher affinity to brain receptors than to peripheral receptors. The heptapeptide, CCK-(26-32) amide, and the tripeptide, CCK-(31-33), are known to antagonize CCK action at peripheral receptors. The heptapeptide bound to central receptors 25 times more potently than a known peripheral antagonist, dibutyryl cyclic GMP. Thus these peptides may act centrally to oppose CCK-8 mediated functions.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / metabolism*
  • Bucladesine / pharmacology
  • Guinea Pigs
  • In Vitro Techniques
  • Kinetics
  • Male
  • Membranes / metabolism
  • Receptors, Cell Surface / metabolism*
  • Receptors, Cholecystokinin
  • Sincalide / metabolism*
  • Structure-Activity Relationship
  • Synaptosomes / metabolism


  • Receptors, Cell Surface
  • Receptors, Cholecystokinin
  • Bucladesine
  • Sincalide