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, 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.
Bungo
T
T
Division of Animal and Marine Bioresources Science, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka, Japan.
Shimojo
M
M
Masuda
Y
Y
Saito
N
N
Sugahara
K
K
Hasegawa
S
S
Furuse
M
M
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000831:Animals, Newborn; D002645:Chickens; D004435:Eating / Q000187:drug effects*; D005934:Glucagon / Q000378:metabolism / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006639:Histidine / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D011498:Protein Precursors / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000378:metabolism
D010446:Peptide Fragments; D011498:Protein Precursors; C055453:glucagon-like peptide 1 (7-36)amide; D014443:Tyrosine; D006639:Histidine; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon