Effects of substitution of n-terminal amino acid of glucagon-like peptide-1 (7-36) amide on food intake of the neonatal chick

Glucagon-like peptide-1 (GLP-1), a member of glucagon superfamily, is synthesized from a large precursor, preproglucagon, and has been postulated to be a novel incretin. Recently, it was reported that central administration of GLP-1 (7–36) amide decreased food intake in rats and chickens. Generally,...

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Bibliographic Details
Published in:Life sciences (1973) 1999, Vol.65 (24), p.PL295-PL299
Main Authors: Bungo, Takashi, Shimojo, Masataka, Masuda, Yasuhisa, Saito, Noboru, Sugahara, Kunio, Hasegawa, Shin, Furuse, Mitsuhiro
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Amino Acid Substitution
Animals
Animals, Newborn
Chickens
Eating - drug effects
food intake
Glucagon - metabolism
Glucagon - pharmacology
Glucagon-Like Peptide 1
glucagon-like peptide-2
Glucagon-Like Peptides
Histidine - metabolism
Injections, Intraventricular
intracerebroventricular administration
Male
Molecular Sequence Data
N-terminal
Peptide Fragments - metabolism
Peptide Fragments - pharmacology
Protein Precursors - metabolism
Protein Precursors - pharmacology
Structure-Activity Relationship
substitution
Tyrosine - metabolism
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Summary:Glucagon-like peptide-1 (GLP-1), a member of glucagon superfamily, is synthesized from a large precursor, preproglucagon, and has been postulated to be a novel incretin. Recently, it was reported that central administration of GLP-1 (7–36) amide decreased food intake in rats and chickens. Generally, the amino acid sequences of the glucagon superfamily members except for gastric inhibitory peptide and growth hormone-releasing factor are identical at N-terminal histidine. It is well known that the GLP-1 receptor is highly specific for GLP-1 and does not bind other peptides of the glucagon superfamily. The aim of this study was to elucidate whether central injection of substituted GLP-1 in which N-terminal histidine of mammalian GLP-1 (7–36) amide was replaced with tyrosine, inhibits food intake in the chick. Intracerebroventricular administration of substituted GLP-1 inhibits food intake in the chick, although the effect of substituted GLP-1 was 11 to 13 fold less than that of mammalian GLP-1 (7–36) amide. These results indicate that N-terminal histidine of GLP-1 (7–36) amide is important for efficacy, but not essential for its bioactivity.
ISSN:0024-3205
1879-0631
DOI:10.1016/S0024-3205(99)00535-4