Cyclic cholecystokinin analogues with high selectivity for central receptors

Journal Article · Mon Feb 29 23:00:00 EST 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.6.1968· OSTI ID:6829121

Charpentier, B; Pelaprat, D; Durieux, C; Dor, A; Roques, B P ^[1]; Reibaud, M; Blanchard, J C ^[2]

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1. Institut National de la Sante et de la Recherche Medicale, Paris (France)
2. Rhone-Poulenc Sante, Vitry-sur-Seine (France)

Taking as a model the N-terminal folding of the cholecystokinin tyrosine-sulfated octapeptide deduced from conformational studies, two cyclic cholecystokinin (CCK) analogues were synthesized by conventional peptide synthesis. The binding characteristics of these peptides were investigated on brain cortex membranes and pancreatic acini of guinea pig. Compounds I and II were competitive inhibitors of ({sup 3}H)Boc(Ahx{sup 28,31})CCK-(27-33) binding to central CCK receptors and showed a high degree of selectivity for these binding sites. This high selectivity was associated with a high affinity for central CCK receptors. Similar affinities and selectivities were found when {sup 125}I Bolton-Hunter-labeled CCK-8 was used as a ligand. Moreover, these compounds were only weakly active in the stimulation of amylase release from guinea pig pancreatic acini and were unable to induce contractions in the guinea pig ileum. The two cyclic CCK analogues, therefore, appear to be synthetic ligands exhibiting both high affinity and high selectivity for central CCK binding sites. These compounds could help clarify the respective role of central and peripheral receptors for various CCK-8-induced pharmacological effects.

• OSTI ID: 6829121
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 85:6; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
CHEMICAL REACTIONS
CROSS-LINKING
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
ELECTROPHORESIS
GUINEA PIGS
HYDROGEN COMPOUNDS
INHIBITION
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
KINETICS
KININS
LABELLED COMPOUNDS
LIGANDS
MAMMALS
MEMBRANE PROTEINS
MOLECULAR STRUCTURE
NERVOUS SYSTEM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDES
POLYMERIZATION
POLYPEPTIDES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RODENTS
TRITIUM COMPOUNDS
VERTEBRATES