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Previous blind studies have shown an increased rate of healing of both duodenal and gastric ulcers following 4 weeks peroral administration of 50 mg trimipramine. The present study shows the effect of 50 mg trimipramine perorally on gastric secretion in relation to that of 25 mg of the drug and placebo. At regular intervals blood specimens were obtained for determination of the serum concentration of trimipramine. In 9 healthy young students it was found that the estimated stabilized values of volume and acid output following 50 mg trimipramine, 33 ml and 3.9 mmol/15 min, respectively, were significantly lower than those following the smallest dose, 37 ml and 4.6 mmol/15 min, respectively. On the other hand, no significant changes of gastric secretion were observed following the peroral administration of 25 mg trimipramine when compared to placebo. Following 50 mg trimipramine the output of pepsin was reduced by about 25%. The values of serum concentration of trimipramine were about 200 nmol/1 at 100 min after administration of 50 mg trimipramine and decreased gradually, whereas the values following the smaller dose were about half of those after the larger one. The results indicate that about 50 mg trimipramine is needed for obtaining a reduction of gastric secretions. Future studies may show whether 25 mg trimipramine, which does not suppress acid secretion when given perorally, is able to promote peptic ulcer healing.

In the present study a comparison was made of the effect of increasing doses of trimipramine (0.05, 0.10, 0.20, 0.40 mg/kg/h), atropine (7, 14, 21, 28 microgram/kg/h), and cimetidine (0.3, 0.6, 1.2, 2.4 mg/kg/h) on the gastric secretion stimulated by 3 microgram/kg/h of histamine dihydrochloride as continuous infusion, each dose step lasting 30 min. In nine healthy individuals it was found that trimipramine had a stimulating effect on the volume and output of acid during one of eight 15-min periods. The largest dose of atropine caused a reduction of the volume and acid output by 68% and 77%, respectively, whereas cimetidine reduced the volume by 74% and the acid output by 89% during the last five 15-min periods, thus having the most pronounced effect. The study may suggest that the healing effect of trimipramine on peptid ulcer is not linked to the effect on submaximal histamine-stimulated secretion and that a different mechanism of action is probably present for the effect of trimipramine, compared with atropine and cimetidine, on the gastric secretion.

The effect of a small dose of somatostatin (0.05 mg/h) on the gastric secretion of acid, pepsin and Intrinsic Factor (IF) after stepwise increases in the dose of pentagastrin was examined in six healthy volunteers. The gastric secretion of acid, pepsin and IF in response to pentagastrin was significantly reduced by a continuous infusion of somatostatin. The pattern of inhibition indicates that somatostatin is a competitive inhibitor of pentagastrin in the stimulation of gastric secretion of both acid, pepsin and IF. This finding supports the hypothesis of a direct effect of somatostatin on the exocrine secretory cells of the stomach.

A Levine tube was placed under radiological control in the stomach, and a thin polyethylene tube in the proximal jejunum of 6 healthy volunteers. The stomach and proximal part of jejunum were perfused for 2 hours with 1% acetylcholine, 20% meat extract (Bovril), and 15% liver extract (LE) alone and in combination with simultaneous infusion of different doses of exogenous pentagastrin intravenously. A significant increase in serum gastrin concentration was found with antral perfusion of LE only, whereas perfusion of the proximal jejunum did not change the basal level of the serum gastrin concentration. No change from control values was observed in gastric acid, and pepsin output on perfusing proximal jejunum with LE alone, or in combination with pentagastrin. Reflux to the stomach varied between 0-1.4%, as determined by addition of radioactive B12 to the perfusates. The experiments showed that gastrin was released from the antrum of the stomach by perfusion with 15 per cent LE, but not from the jejunum under the present experimental conditions. In the present experiments Bovril and acetylcholine perfusions did not cause significant responses from the antrum or from the proximal jejunum.

The gastric secretion of IF, acid, and pepsin during basal conditions and stimulation by pentagastrin decreased significantly in 8 unoperated duodenal ulcer patients following administration of atropine. The basal concentrations of acid and pepsin decreased, whereas that of IF remained unchanged. An increase of plasma gastrin concentration from the basal value was observed after injection of atropine alone. The secretions of IF and acid decreased significantly from the pre-operative values after proximal gastric vagotomy in 7 duodenal ulcer patients. The basal IF output decreased by 19.8 per cent and the stimulated output by 41.4 per cent. The basal and stimulated secretions of acid decreased by 50.0 and 44.1 per cent, respectively. It is suggested that the smaller reduction of IF than of acid may be of importance for the vitamin B12 absorption after vagotomy. The decreased secretion of IF was secondary to the reduction of volume both after'medical' and surgical vagotomy.

The effect os somatostatin (0.6 mg/hour) on insulin-stimulated gastrin release and gastric secretion of acid, pepsin, and IF has been examined in 6 unoperated patients with duodenal ulcer. Gastrin release and gastric secretion of acid, pepsin, and IF in response to insulin alone (0.15 IU/kg bw. iv.) were significantly reduced by simultaneous administration of somatostatin. This finding indicates an inhibitory effect of somatostatin on insulin-induced gastrin release and gastrin secretion in addition to the already known effects of somatostatin.

Gastric secretion (volume, pepsin and acid output) was measured in the basal state and during graded doses of intravenous pentagastrin (0.02, 0.2 and 2 micrograms/kg/h) in 5 patients with moderate to severe renal failure. On one occasion they also received intravenous cimetidine (1.5 mg/kg bolus followed by 0.5 mg/kg/h). Sustained cimetidine concentrations of approximately 2 micrograms/ml (8 nmol/ml) were associated with a 75-90% inhibition of stimulated acid output, reflecting both a reduction in volume and a lower acid concentration. Pepsin output was less depressed by cimetidine, as the pepsin concentration of the gastric juice actually increased in response to combined pentagastrin and cimetidine administration. It is concluded that renal failure, although affecting cimetidine pharmacokinetics, does not appreciably alter the response to the drug.

Intravenous infusions of carbachol and pentagastrin were given separately or simultaneously in 6 healthy students. The volume of gastric secretion and the concentration and output of acid, pepsin, and IF increased significantly during infusion of carbachol alone, whereas the plasma gastrin concentration remained unchanged. Carbachol had no effect on the acid, pepsin, and IF secretion by pentagastrin. The results indicate an effect of carbachol on acid, pepsin, and IF secretion, independent of changes in plasma gastrin concentration. No synergistic or potentiating effect was demonstrated between carbachol and pentagastrin.

The gastric secretion of acid was examined 30 minutes basally (BAO) and in response to stepwise increasing doses of pentagastrin in subjects with (n = 51) and without (n = 40) peptic ulcer disease. None of them showed basal anacidity. Before insertion of the gastric tube, blood was taken for radioimmunological determination of the serum gastrin concentration (SG). A significant positive correlation was found between SG and BAO in the subjects without ulcer. This was mainly due to a close correlation in 20 healthy young volunteers. When BAO and SG was expressed as proportions of calculated maximal acid response (Vmax) and half maximal dose of pentagastrin (Km), respectively, the positive correlation between SG and BAO was improved and reached significance also in the individuals with peptic ulcer disease. The findings suggest that the serum concentration of gastrin plays a role in the basal gastric secretion.

In animals massive resection of the small intestine is followed by increased gastric acid secretion and an increase in serum gastrin levels. Whether hypersecretion occurs in man after intestinal resections or intestinal bypass is unclear, but an increase in fasting gastrin levels has been reported after intestinal resection. In this series a significant increase in basal gastric acid secretion and fasting serum gastrin levels has been demonstrated after intestinal bypass. However, none of the patients developed peptic ulcer or clinical symptoms of hypersecretion after the bypass operation. Whether the increase in basal secretion and the serum gastrin concentration are interrelated or of any clinical importance is uncertain.

Three experiments were carried out in each of 6 healthy students on separate days, in a randomized order. Intravenous saline infusions were given for one hour basally in each experiment. During the second hour either pentagastrin, pentagastrin and somatostatin, or somatostatin alone were given. Gastric juice was collected continuously during all experiments. Somatostatin decreased the volume of gastric secretion and the concentrations of acid and pepsin, and output of acid, pepsin, and intrinsic factor (IF). The plasma gastrin concentration was not changed by somatostatin. A rebound effect was seen on pepsin and IF outputs after cessation of somatostatin, and on blood sugar concentration. The present study suggests that somatostatin acts on gastric secretion either directly or by mechanisms other than by inhibition of gastrin. The rebound of pepsin and IF indicates a release-inhibiting action on these substances similar to the effect of somatostatin on the release of some hormones.

The stomachs of 8 healthy volunteers were intubated with a Levine tube under radiological control. In addition, a thin polyethylene tube was placed in the proximal duodenum. After a 1-hour period with no perfusion, the duodenum was perfused for two hours with 15% liver extract (LE) (pH 4.5--5.5; 1027 mosm/kg water) at a rate of 100 ml/hour either alone or in combination with intravenous infusion of different doses of exogenous pentagastrin. All subjects were also tested with the tubes in place for 3 hours, but with no perfusion or pentagastrin. Reflux to the stomach was monitored by addition of radioactive B12 to the perfusates. Plasma gastrin, gastric acid, and pepsin were measured in 15-minute periods. During perfusion of the proximal duodenum, where reflux of the perfusates was less than 4%, only a slight and inconstant change in plasma gastrin was seen. Gastric acid and pepsin outputs were increased to approx. 18% and 25% of the maximal pentagastrin stimulation respectively. Whereas 15% LE was shown to release gastrin by antral perfusion however, such release was not found by duodenal perfusion, except where reflux to the antrum was seen. The results suggest that intestinal stimulation of gastric secretion exists, but has not been found to be gastrin dependent in the present investigation.