Structure-activity relationship studies on cholecystokinin: Analogues with partial agonist activity

Journal Article · Mon Feb 01 00:00:00 EST 1988 · American Journal of Physiology; (USA)

OSTI ID:6810177

Galas, M C; Lignon, M F; Rodriguez, M; Mendre, C; Fulcrand, P; Laur, J; Martinez, J ^[1]

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1. Centre de Pharmacologie-Endocrinologie, Montpellier (France)

In the present study, hepta- and octapeptide analogues of the C-terminal part of cholecystokinin, modified on the C-terminal phenylalanine residue, were synthesized. CCK analogues were prepared in which the peptide bond between aspartic acid and phenylalanine had or had not been modified and were lacking the C-terminal primary amide function. These CCK derivatives were able to cause full stimulation of amylase release from rat pancreatic acini but without a decrease in amylase release at supramaximal concentrations. There was a close relationship between the abilities of these derivatives to stimulate amylase release and their abilities to inhibit binding of {sup 125}I-BH-CCK-9 to CCK receptors on rat and guinea pig pancreatic acini. These CCK analogues were also able to recognize the guinea pig brain CCK receptors, some of them being particularly potent. The findings indicate that the aromatic ring of phenylalanine is important for the binding to brain and pancreatic CCK receptors, whereas the C-terminal primary amide function is not essential for the binding to pancreatic CCK receptors but is crucial for biological activity of rat pancreatic acini.

• OSTI ID: 6810177
• Journal Information: American Journal of Physiology; (USA), Vol. 254:2; ISSN 0002-9513
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
KININS
ENZYME ACTIVITY
PROTEIN ENGINEERING
RECEPTORS
STRUCTURE-ACTIVITY RELATIONSHIPS
PHENYLALANINE
BIOCHEMICAL REACTION KINETICS
AMYLASE
ASPARTIC ACID
BRAIN
CYAM PROCESS
DERIVATIZATION
GASTRIN
GUINEA PIGS
IODINE 125
LABELLING
PANCREAS
PEPTIDES
PROTEIN STRUCTURE
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CHEMICAL REACTIONS
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
ELECTRON CAPTURE RADIOISOTOPES
ENDOCRINE GLANDS
ENZYMES
GLANDS
GLYCOSYL HYDROLASES
HORMONES
HYDROLASES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPES
KINETICS
MAMMALS
MANAGEMENT
MEMBRANE PROTEINS
NERVOUS SYSTEM
NUCLEI
O-GLYCOSYL HYDROLASES
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
POLYPEPTIDES
PROCESSING
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RODENTS
VERTEBRATES
WASTE MANAGEMENT
WASTE PROCESSING
550201* - Biochemistry- Tracer Techniques