Bombesin-induced tachyphylaxis markedly enhances gastrin response to a meal

This study was designed to determine whether a bombesinlike peptide mediated the gastrin response to food. Tachyphylaxis of gastrin release was induced in six dogs by prolonged infusion of bombesin (500 ng X kg-1 X h-1) before ingestion of a meal. An impaired postprandial gastrin response during bombesin tachyphylaxis would be indirect evidence that a bombesinlike peptide mediated the gastrin response to food. Serum gastrin concentrations peaked (74 +/- 18 pM) 1 h after commencement of the bombesin infusion and then fell significantly (P less than 0.01), reaching a nadir of 15 +/- 1 pM at 4 h. Dogs were then fed the standard meal (15 g/kg Prime dog food), and the serum gastrin response was compared with that observed in response to the meal ingested during saline infusion. There was sixfold enhancement (P less than 0.01) of meal-stimulated gastrin release during bombesin infusion compared with saline infusion. Stopping the bombesin infusion before ingestion of the meal still resulted in significant (P less than 0.05) enhancement of the meal response. Although pancreatic polypeptide responses to bombesin also exhibited tachyphylaxis, prolonged infusion of bombesin did not enhance the pancreatic polypeptide response to food. We conclude that a bombesinlike peptide does not mediate the gastrin response to food in dog. We speculate that bombesin stimulates both secretion and synthesis of gastrin but that only secretion is subject to tachyphylaxis. The enlarged secretory pool produces an enhanced response when the G cell is exposed to stimulants other than bombesin.