Structure-activity relationship studies on cholecystokinin: Analogues with partial agonist activity
- 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), Journal Name: American Journal of Physiology; (USA) Vol. 254:2; ISSN 0002-9513; ISSN AJPHA
- Country of Publication:
- United States
- Language:
- English
Similar Records
Carbobenzoxy amino acids: Structural requirements for cholecystokinin receptor antagonist activity
Preparation of biologically active radioiodinated cholecystokinin for radioreceptor assay and radioimmunoassay
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
AMYLASE
ANIMALS
ASPARTIC ACID
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CHEMICAL REACTIONS
CYAM PROCESS
DAYS LIVING RADIOISOTOPES
DERIVATIZATION
DIGESTIVE SYSTEM
ELECTRON CAPTURE RADIOISOTOPES
ENDOCRINE GLANDS
ENZYME ACTIVITY
ENZYMES
GASTRIN
GLANDS
GLYCOSYL HYDROLASES
GUINEA PIGS
HORMONES
HYDROLASES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
KINETICS
KININS
LABELLING
MAMMALS
MANAGEMENT
MEMBRANE PROTEINS
NERVOUS SYSTEM
NUCLEI
O-GLYCOSYL HYDROLASES
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PANCREAS
PEPTIDE HORMONES
PEPTIDES
PHENYLALANINE
POLYPEPTIDES
PROCESSING
PROTEIN ENGINEERING
PROTEIN STRUCTURE
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RODENTS
STRUCTURE-ACTIVITY RELATIONSHIPS
VERTEBRATES
WASTE MANAGEMENT
WASTE PROCESSING