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.