Potentiation effect of cholecystokinin-octapeptide on pancreatic bicarbonate secretion stimulated by a physiologic dose of secretin in humans.

We studied the potentiation effect of cholecystokinin-octapeptide and secretin on pancreatic secretion of bicarbonate and trypsin in humans. The pancreatic bicarbonate and trypsin outputs were determined by using a triple-lumen duodenal tube and indicator dilution technique while gastric juice was completely aspirated. When cholecystokinin-octapeptide in varied doses, 2.6, 5.3, 10.9, 26.3, 52.6, and 109.4 pmol . kg-1 . h-1, was added to i.v. infusion of secretin in a physiologic dose, 0.03 clinical units (CU) . kg-1 . h-1, the bicarbonate outputs were significantly greater than those achieved by secretin or cholecystokinin-octapeptide alone or the sum of the bicarbonate outputs produced by each hormone. The potentiation effect of cholecystokinin-octapeptide occurred at the dose of 10.9 pmol . kg-1 . h-1. No further further augmentation on the bicarbonate output occurred when the dose of cholecystokinin-octapeptide was increased in the dose range greater than 10.9 pmol . mg-1 . h-1. No potentiation on pancreatic secretion of trypsin was apparent when the two hormones were given simultaneously. Thus, cholecystokinin-octapeptide in a relatively small dose range potentiated the pancreatic bicarbonate secretion stimulated by a physiologic dose of secretin. The pancreatic enzyme secretion does not appear to be potentiated by two hormones.

Effects of atropine on the action and release of secretin in humans.

Using two groups of volunteers, we investigated the effects of atropine on pancreatic secretion of bicarbonate, protein, and trypsin stimulated by secretin. Secretin given intravenously in graded doses of 0.03, 0.06, and 0.125 clinical units.kg-1.h-1 produced significant increases in pancreatic secretion of bicarbonate in a dose-related manner. Pancreatic secretion of bicarbonate and protein was significantly suppressed by intravenous atropine, despite the dose of secretin infused. Intrajejunal perfusion of HCl at a rate of 3.3 mM/h, producing plasma secretin concentration comparable with that of the postprandial state, resulted in significant increases in the pancreatic secretion of bicarbonate. The increase in the pancreatic secretion of bicarbonate and trypsin was significantly suppressed by atropine. However, atropine did not affect the increase in the plasma secretin concentration produced by jejunal acidification or intravenous secretin. These studies indicate that atropine inhibits the pancreatic effect but not the intestinal release of secretin.

Plasma secretin concentrations and gastric pH in healthy subjects and patients with digestive diseases.

Plasma secretin concentrations were determined in healthy subjects and patients with duodenal ulcer, achlorhydria, and celiac sprue. Mean fasting plasma secretin concentrations in 26 healthy subjects and 26 duodenal ulcer patients were 6.7 +/- 0.5 and 10.2 +/- 1.2 pg/ml, respectively, and were significantly different (P less than 0.02). After ingestion of a standard meat meal, pyloric pH decreased to less than 4.5 within 15 min and plasma secretin concentrations significantly increased in all 52 subjects. In 14 subjects (seven healthy subjects and seven patients with duodenal ulcer), no significant rise in plasma secretin concentration occurred when pyloric pH was maintained at greater than 5.0 by intravenous cimetidine (600 mg) and intragastric antacid. In 10 achlorhydric patients, intragastric pH remained greater than 5.0 after the meal and plasma secretin concentrations did not change. However, plasma secretin concentrations increased significantly when 0.1 N HCl was infused in the stomach (25 mEq/hr) during the postprandial period. In all eight adult patients with celiac disease (seven untreated, one partially treated), pyloric pH remained less than 4.0 after a meal. Postprandial secretin concentrations did not increase significantly in six and showed a transient rise in two. These studies show that (1) plasma secretin concentration increases significantly after meals in healthy subjects and patients with duodenal ulcer; (2) neutralization of gastric acid and the achlorhydric state show no significant postprandial rise in plasma secretin concentration; (3) achlorhydric patients do not have a defect in secretin release in response to acid; and (4) failure of postprandial rise in plasma secretin in patients with celiac disease is attributed to impaired release of secretin and in achlorhydric patients it is attributed to lack of acid secretion.

Methyldopa-induced pancreatitis.

An acute febrile illness associated with gastrointestinal upset developed in a patient within one week after starting treatment with methyldopa. The illness was characterized by prompt subsidence of symptoms when the patient withdrew therapy secondary to gastrointestinal upset, and recrudescence of symptoms when methyldopa therapy was reinitiated. This was associated with hyperamylasemia, hyperlipasemia, hyperpyrexia, and epigastric pain, both on admission to the hospital and upon rechallenge with methyldopa. Although gastrointestinal upset has been reported as an untoward side effect of methyldopa, this is the first report to our knowledge of documented methyldopa-induced hyperamylasemia and hyperlipasemia secondary to pancreatitis.