Neurotensin analogs (D-TYR11) and (D-PHE11)neurotensin resist degradation by brain peptidases in vitro and in vivo
Journal Article
·
· J. Pharmacol. Exp. Ther.; (United States)
OSTI ID:6541708
The present study was designed to compare the susceptibility of neurotensin (NT), (/sup 3/H)NT, (D-Tyr11)NT and (D-Phe11)NT to degradation by 1) rat brain synaptic membranes in vitro and 2) after i.c.v. administration in the rat in vivo. Degradation was assessed by purifying the peptides using reverse phase high-performance liquid chromatography and by measuring the amount of radioactive or absorbing (OD 230) material under each peptide peak. In contrast to NT, (D-Tyr11)NT and (D-Phe11)NT were resistant to degradation by brain synaptic peptidases in vitro. Furthermore, NT was rapidly metabolized in brain tissues after i.c.v. administration, whereas (D-Tyr11)NT was metabolically stable. The present data confirm the central role of NT residue Tyr11 in the mechanisms of NT inactivation by brain synaptic peptidases. They account for the higher in vivo potency of (D-Tyr11)NT as compared with its in vitro potency. Finally, they explain, at least in part, the need to administer large doses of NT in the brain in order to observe neurobehavioral and neuropharmacological effects.
- Research Organization:
- Centre National de la Recherche Scientifique, Nice, France
- OSTI ID:
- 6541708
- Journal Information:
- J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 227:3; ISSN JPETA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BODY
BRAIN
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
ENZYMES
HORMONES
HYDROLASES
IN VITRO
IN VIVO
INACTIVATION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANES
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PEPTIDE HYDROLASES
PEPTIDES
PITUITARY HORMONES
PROTEINS
RATS
REACTION KINETICS
RODENTS
STRUCTURE-ACTIVITY RELATIONSHIPS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BODY
BRAIN
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
ENZYMES
HORMONES
HYDROLASES
IN VITRO
IN VIVO
INACTIVATION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANES
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PEPTIDE HYDROLASES
PEPTIDES
PITUITARY HORMONES
PROTEINS
RATS
REACTION KINETICS
RODENTS
STRUCTURE-ACTIVITY RELATIONSHIPS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES