TY - JOUR
T1 - Cholecystokinin-octapeptide fragments
T2 - Binding to brain cholecystokinin receptors
AU - Knight, Martha
AU - Tamminga, Carol A.
AU - Steardo, Luca
AU - Beck, Mary E.
AU - Barone, Paolo
AU - Chase, Thomas N.
PY - 1984/10/1
Y1 - 1984/10/1
N2 - 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.
AB - 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.
KW - Brain receptors
KW - CCK-5, CCK-4, CCK-3
KW - Cholecystokinin antagonists
KW - Cholecystokinin fragments
KW - Cholecystokinin receptors
KW - Guinea pig cortical membrane
KW - N-terminal CCK fragment peptides
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U2 - 10.1016/0014-2999(84)90647-2
DO - 10.1016/0014-2999(84)90647-2
M3 - Article
C2 - 6092115
AN - SCOPUS:0021211934
SN - 0014-2999
VL - 105
SP - 49
EP - 55
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-2
ER -