Effect of gastrin-releasing peptide (GRP1-27), neuromedin-C (GRP18-27), and neuromedin-B on gastrin and somatostatin secretion from the rat stomach

In the present study the effects of gastrin-releasing peptide (GRP1-27), its C-terminal decapeptide neuromedin-C (GRP18-27) and the related peptide neuromedin-B were examined on the secretion of gastrin and somatostatin-like immunoreactivity (SLI) from the isolated perfused rat stomach at intraluminal pH 7 or pH 2. GRP1-27 and GRP18-27 stimulated gastrin secretion equally effective at concentrations of 10(-10), 10(-9), 10(-8), 10(-7) and 10(6)M at luminal pH 7. In addition neuromedin-B was tested at 10(-11), 10(-10), 10(-8) and 10(-6)M and it increased gastrin release similar to equimolar doses of GRP18-27. At luminal pH 2 GRP1-27 stimulated gastrin secretion at 10(-9), 10(-8), 10(-7) and 10(-6)M while GRP18-27 was only effective at 10(-8) and 10(-7)M. Neuromedin-B elicited a gastrin increase at 10(-8)M similar to GRP18-27 and also at 10(-6)M. All three peptides had no significant effect on SLI release at luminal pH 7. At luminal pH 2 GRP1-27 at 10(-9)M and 10(-6)M and GRP18-27 and neuromedin-B at 10(-10)M elicited a significant stimulation of SLI secretion. These data demonstrate that all three bombesin-like peptides GRP1-27, GRP18-27 and neuromedin-B can stimulate gastrin release at either a neutral or an acidic luminal pH, while SLI release is affected only at an acidic intragastric milieu. This suggests that all three forms of bombesin-like peptides are good candidates for the peptidergic regulation of gastrin release in the rat stomach, while their role in somatostatin release seems to be more restricted.