Cholecystokinin-octapeptide fragments: binding to brain cholecystokinin receptors.
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.
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011949:Receptors, Cholecystokinin; D012844:Sincalide / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000378:metabolism
D011956:Receptors, Cell Surface; D011949:Receptors, Cholecystokinin; D003994:Bucladesine; D012844:Sincalide