Actions of novel bombesin receptor antagonists on pancreatic secretion in

Recently synthezised highly specific and potent bombesin receptor antagonist permit study of the role of endogenous bombesin-like peptides in the physiological regulation of pancreatic secretion. We now tested the action of three novel pseudononapeptide bombesin/gastrin releasing peptide (GRP) antagonists (RC-3095, RC-3100 and RC-3120) on amylase release in vitro from isolated rat pancreatic acini and on protein secretion in vivo in chronic pancreatic fistula rats. In isolated pancreatic acini, all three bombesin receptor antagonists inhibited the amylase secretion induced by bombesin by shifting to the right the amylase response to bombesin without altering the maximal response. These antagonists also reduced concentration dependently the near-maximal amylase response to bombesin, the concentration required for 50% reduction (IC 50) being about 10 −7 M for RC-3095 and RC-3100 and 10 −6 M for RC-3120. None of the bombesin/GRP anatagonists used affected the amylase response to CCK, pentagastrin or urecholine. In conscious rate witha chronic pancreatic fistula, all three bombesin antagonists shifted to the right the pancreatic protein response to graded doses of bombesin without changing the maximal response. These antagonists inhibited the protein response to constant background stimulation with bombesin in a dose-dependent manner, the ID 50 being about 20 nmol/kg per h for RC-3095 and RC-3100 and about 160 nmol/kg per h for RC-3120. None of the antagonists significantly affected basal pancreatic secretion or secretion induced by sham-feeding, ordinary feeding or the diversion of pancreatic juice from the duodenum. These results indicate that exogenous bombesin is a potent direct stimulant of pancreatic enzyme secretion. However, the results do not support the view that endogenous bombesin/GRP-like peptides are involved in the physiological regulation of pancreatic secretion in rats

Effects of Cyclic Hexapeptide Analog of Somatostatin on Pancreatic Secretion in Dogs

Abstract The effects of a cyclic hexapeptide analog of somatostatin, [cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe)] (cyclo-SS), administered intravenously (iv) or instilled into the duodenum (id) on the pancreatic response to endogenous (meal and duodenal acidification) and exogenous (secretin, CCK) stimulants were compared in five dogs with esophageal, gastric, and pancreatic fistulae. Cyclo-SS given iv in graded doses against a constant background stimulation with secretin caused a similar and dose-dependent inhibition of pancreatic HCO3 and protein secretion being about twice as potent as somatostatin-14 (SS-14). Cyclo-SS, whether applied topically to the duodenal mucosa in a dose of 1 μg/kg or given iv at a dose of 0.5 μg/kg-hr, resulted in a similar inhibition of pancreatic secretion induced by feeding a meat meal, sham-feeding, duodenal acidification, or infusion of secretin or CCK. The inhibition of pancreatic secretion by cyclo-SS was due in part to direct inhibitory action on the exocrine pancreas as well as to the suppression of the release of secretin, insulin, and pancreatic polypeptide. It is concluded that cyclo-SS is a more potent inhibitor of pancreatic secretion than SS-14 and that it is active when administered both parenterally and intraduodenally

Effect of thyrotropin-releasing hormone on gastro-intestinal secretions in dogs

Thyrotropin-releasing hormone (TRH) immunoreactivity has been shown previously to be distributed throughout the gastrointestinal tract and the pancreas. This study demonstrated that TRH given intravenously suppresses, in a dose-related manner, sham-feeding induced food intake and inhibits gastric secretion provoked by infusion of pentagastrin or instillation of 10% liver extract into the stomach. TRH also reduces pancreatic response to secretin, caerulein, feeding a meat meal or duodenal acidification. The findings that TRH inhibits gastric and pancreatic secretions induced by exogenous and endogenous stimulants, and that the inhibition by TRH of post-prandial secretion is not accompanied by any change in serum gastrin, indicate that TRH probably acts directly on the exocrine stomach and pancreas