Effects of substance P and other peptides on the release of somatostatin, insulin, and glucagon in vitro.

We studied the actions of substance P, bombesin, vasoactive intestinal peptide (VIP), and the octapeptide of cholecystokinin (CCK-8-S) on the release of somatostatin, insulin, and glucagon from the isolated perfused pancreatico-duodenal canine preparation. Substance P at concentrations ranging from 0.2-5.0 nM stimulated the secretion of somatostatin, insulin, and glucagon in a dose-dependent manner. However, the responses evoked by substance P were modified by the prevailing glucose level; higher somatostatin and insulin and lower glucagon responses were obtained at the high glucose concentration of 8.3 mM rather than at the low glucose concentration of 2.8 mM. At a glucose concentration of 5.5 mM, somatostatin release was above the prestimulation level in response to 1 nM substance P (89 +/- 15%; P less than 0.01), VIP (49 +/- 7%; P less than 0.01), or CCK-8-S (99 +/- 21%; P less than 0.01); bombesin was without effect (16 +/- 14; P = NS). Insulin release was enhanced by substance P (150 +/- 45%; P less than 0.05), bombesin (162 +/- 56%; P less than 0.05), VIP (44 +/- 5%; P less than 0.01), and CCK-8-S (190 +/- 17%; P less than 0.001). Furthermore, a significant release of glucagon was evoked by 1 nM substance P (501 +/- 158%; P less than 0.05), bombesin (30 +/- 10%; P less than 0.05), VIP (43 +/- 8%; P less than 0.01), or CCK-8-S (140 +/- 19%; P less than 0.001).