Effects of neuromedin B, gastrin-releasing peptide-10 and their fragment peptides on secretion of gastrointestinal and pancreatic hormones in dogs.
The effects of neuromedin B (NMB), gastrin-releasing peptide (GRP)-10 and their C-terminal fragment peptides on the pancreatic and gastrointestinal hormone release were studied in dogs. Intravenous bolus injections of NMB and GRP-10 (4.5 nmol/kg) into conscious dogs elicited a sharp and statistically significant rise in plasma gastrin and insulin levels, but only GRP-10 brought on a significant rise in the plasma glucagon and enteroglucagon levels. The degree of stimulation of gastrin and insulin secretion by NMB and GRP-10 was dose-dependent. With a dose of 4.5 nmol/kg, the minimum size of C-terminal fragment peptides of NMB and GRP-10 to stimulate gastrin secretion was NMB and GRP-10, respectively. Both NMB and GRP-10 (0.1-100 nmol/l) stimulated insulin release from the isolated canine pancreas. The glucagon release was stimulated by 10 and 100 nmol/l GRP-10 and was not stimulated by the same doses of NMB. The somatostatin release was not influenced by either peptide. It is concluded that 1) NMB and GRP-10 can stimulate gastrin and pancreatic hormone secretion, and the latter effect may be mainly due to a direct action on the islet cells; 2) the stimulatory effect of GRP-10 is stronger than that of NMB. The difference in the minimal active fragment between NMB and GRP-10 suggests that the amino acid of position 3 - NMB (Leu) and GRP-10 (His) - may play an important role in their biological activity.
Kawai
K
K
Institute of Clinical Medicine, University of Tsukuba, Ibaraki-ken, Japan.
Chiba
Y
Y
Mukai
H
H
Munekata
E
E
Yamashita
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001839:Bombesin / Q000494:pharmacology*; D004285:Dogs; D005755:Gastrins / Q000378:metabolism*; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D005934:Glucagon / Q000378:metabolism*; D004763:Glucagon-Like Peptides / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D015287:Neurokinin B / Q000031:analogs & derivatives*; D009479:Neuropeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D001786:Blood Glucose; D005755:Gastrins; D005768:Gastrointestinal Hormones; D007328:Insulin; D009479:Neuropeptides; D010446:Peptide Fragments; D004763:Glucagon-Like Peptides; C040794:neuromedin C; D015287:Neurokinin B; C038393:neuromedin B; D005934:Glucagon; D001839:Bombesin