SUMMARY Gastric acid and serum gastrin, pancreatic polypeptide, and insulin responses to cephalic vagal stimulation were studied in eight patients with duodenal ulcer using modified shamfeeding for periods varying from four to 30 minutes. In addition, the maximal acid response to sham-feeding was compared with that induced by pentagastrin in 10 healthy subjects and 14 patients with duodenal ulcer. It was found that the gastric acid response to modified sham-feeding reached the maximal value after 15 minutes of sham-feeding and amounted to about 68% of the pentagastrin maximum. The serum pancreatic polypeptide response was also increased after modified sham-feeding and depended on the duration of this procedure, whereas gastrin and insulin responses were not significantly affected by modified sham-feeding. When the peak acid output induced by modified sham-feeding was normalised as percentage of the peak response to pentagastrin, it was similar in healthy subjects and in patients with duodenal ulcer; this indicates that the increased peak acid response to modified sham-feeding observed in patients with duodenal ulcer corresponded with their greater parietal cell mass rather than with increased vagal tone.It is well established that the physiological vagal excitation accomplished by the 'chew and spit' technique results in a potent gastric secretory stimulation1 3 accompanied by a rise in plasma hormonal levels.3 7 The gastric acid secretory rate achieved by this modified sham feeding in duodenal ulcer patients was found to be of similar range to that attained by adequate sham-feeding,8 but no study was performed to determine the relationship between the duration of the modified sham-feeding and the gastric secretory response. In dogs, it has been shown that a marked gastric secretion occurred after less than one minute of sham-feeding and that when the duration of sham-feeding was extended there was a further increase in gastric secretion9 and proportional increments in plasma gastrin or insulin levels were observed.5 The maximal acid response to shamfeeding in these animals was not significantly different from that achieved by gastrin.9 No similar studies have been so far performed in man, although the modified sham-feeding has been widely used to study vagal control of gastric secretion.*Address for correspondence: Professor Dr SJ Konturek, Institute of Physiology, 31-531 Krak6w, ul. Grzegorzecka 16, Poland.Received for publication 16 May 1981 This study was designed to determine the relationship between the duration of the modified sham-feeding and the gastric secretory and plasma hormonal responses to this procedure and to compare the maximal gastric acid response to modified sham-feeding and to pentagastrin in healthy subjects and duodenal ulcer patients. Methods SUBJECTSTen healthy male subjects (mean age 20 years, range 19-22 years; mean weight 71 kg, range 66-77 g) and 20 male patients (age 20 years, range 19-23 years; mean weight 68 kg, range 61-75 kg) with wellestablished chronic duodenal ulcer disea...

This study was designed to test the effects of pentagastrin and epidermal growth factor (EGF) on stress-induced ulceration and on the antral content of gastrin and somatostatin (SLI) in rats. Four groups of 14 to 15 rats had been prepared for 7 days by one of the following methods: saline injection (control); injection of pentagastrin (250 micrograms/kg, 3 times/day); injection of EGF (10 micrograms/kg, 3 times/day); or injection of EGF plus pentagastrin. At the end of the treatment period, half of each group of rats were sacrificed (nonstress group). There were no ulcers in the nonstress control groups of rats. Stress was applied by water immersion in the remaining half of the rats. The injections of pentagastrin and/or EGF resulted in substantial increase in antral content of SLI. After 20 hours of stress, the ulcer index was 40.5 +/- 3.3 in the controls, compared to 6.4 +/- 1.2 and 16.2 +/- 2.3 in rats that received pentagastrin or EGF, respectively. Injections of both pentagastrin and EGF resulted in an ulcer index of 26.2 +/- 2.0, which was significantly lower than that in controls, but higher than that in rats treated with either peptide alone. The stress resulted in significant decrease in antral SLI in all groups of rats, whereas SLI content in rats treated with pentagastrin and/or EGF remained significantly higher than that of controls. Antral content of gastrin did not differ significantly in the four groups tested. The ulcer index was inversely correlated with antral SLI content. We confirm and extend previous observations that pentagastrin and EGF prevent stress ulcer formation, and suggest that endogenous SLI may account, at least in part, for their antiulcer activity.

The effect of somatostatin, a growth hormone releasing-inhibiting hormone (GH-RIH) on basal and meal-, pentagastrin-, or histamine-stimulated gastric acid and pepsin secretion was studied in six duodenal ulcer patients. Intravenous GH-RIH infused in graded doses ranging from 0.62 to 5.0 microgram/kg/hr produced a dose-related inhibition of pentagastrin-induced acid secretion reaching about 15% of control level at the dose of 5.0 microgram/kg/hr. Acid inhibition was paralleled by a decrease in the pepsin output and accompanied by a dose-dependent reduction in serum growth hormone and insulin levels measured by radioimmunoassay. GH-RIH used in a single dose of 2.5 microgram/kg/hr produced about 85% inhibition of acid secretion induced by a meal (measured by intragastric titration) accompanied by a significant decrease in serum gastrin and insulin levels. The effect of GH-RIH on histamine-stimulated secretion was very modest and observed only after stopping the GH-RIH infusion. Thus GH-RIH suppressed acid and pepsin secretion induced by pentagastrin and a meal, and this effect was accompanied by a suppression of serum growth hormone and gastrin levels which may contribute to the inhibition of gastric secretion observed.

We investigated the effects of luminal application of graded concentrations of conventional mucosal barrier breakers such as ethanol, aspirin (ASA), and sodium taurocholate (TCh), as well as 16,16-dimethyl prostaglandin E2 (DMPGE2) on gastric alkaline output (GAO) and transmucosal potential difference (PD). The Lucite chamber stomach-flap preparation was used in 50 dogs whose basal H+ secretion was inhibited by intravenous cimetidine. Graded concentrations of ethanol, and TCh at pH 5.0, and acidified solutions of ASA (at pH 5.0--2.0) were found to produce a dose-dependent increase in GAO accompanied by a stepwise decline in PD. Increasing concentrations of DMPGE2 above 1.0 microgram/ml caused a dose-related increase in GAO and a reduction in PD. The combination of DMPGE2 with ethanol aggravated the PD changes, whereas GAO induced by these agents was decreased. Alterations in GAO and PD evoked by the ASA solutions varying in pH were not significantly affected by the addition of 1.0 microgram/ml DMPGE2 to the bathing fluid. These results indicate that stimulation of gastric alkalinization with concomitant fall in PD is a common feature for various mucosa-irritant substances, and pretreatment with DMPGE2 does not prevent these effects.

1. Gastric acid and pancreatic bicarbonate and protein secretion as well as immunoreactive serum gastrin and pancreatic polypeptide concentrations in response to a meal and secretin have been measured before and after infusion of bovine pancreatic polypeptide or its C-terminal hexapeptide. 2. Liver extract meal kept in the stomach at pH 5.5 (by intragastric titration) produced a marked increase in gastric acid and pancreatic protein secretion accompanied by a rise in serum gastrin and pancreatic polypeptide levels. Exogenous bovine pancreatic polypeptide caused little change in gastric secretion and serum gastrin but resulted in a profound suppression of pancreatic secretion. 3. Ordinary feeding a liver meal produced a marked increase in pancreatic bicarbonate and protein secretion that was dose-dependently inhibited by bovine pancreatic polypeptide or its C-terminal hexapeptide, the degree of inhibition being closely correlated with the increments in plasma pancreatic polypeptide. 4. Bovine pancreatic polypeptide and its C-terminal hexapeptide also inhibited secretin and caerulein-induced pancreatic secretion in a dose-dependent manner. 5. This study shows that bovine pancreatic polypeptide inhibits pancreatic secretion at least in part by acting directly on the exocrine pancreas and that its biological activity resides in its C-terminal hexapeptide fragment.