J. De Graef

Antral Gastrin Cell Proliferation after Vagotomy in Rats

The total number of antral gastrin cells, the antral surface area and the serum gastrin concentration were determined in two groups of rats. The animals had been submitted at random either to vagotomy and pyloroplasty or to pyloroplasty alone 3 weeks before. The indirect immunoperoxidase reaction and a direct quantitative histological method were used to count the gastrin cells. Radioimmunoassay was used to estimate the serum gastrin concentration. The total number of gastrin cells in the stomach was 52% (p less than 0.01) more elevated in the vagotomized animals. Both antral mucosal surface and calculated concentration of gastrin cells per square millimeter of mucosa were significantly higher (0.01 less than p less than 0.05) in this group of animals. The serum gastrin values were significantly (p less than 0.01) more elevated after vagotomy. These observations indicate that vagotomy may induce an antral gastrin cell hyperplasia which could explain in part the hypergastrinemia observed after this surgical procedure.

Direct Method for Estimating the Total Gastrin Cell Number in the Stomach of Rats

An original and simple method for counting the total G cell number in the stomach of small rodents is described. Staining the G cells with the peroxidase-antibody technique and counterstaining the nucleus make it possible to correct the nuclear overestimation. Counting directly the total number of G cells in sections from the entire stomach avoids errors due to tissue retraction and to unprecise delineation of the antro-fundic limit.

Effects of morphine, enkephalins and naloxone on postprandial gastric acid secretion, gastric emptying and gastrin release in dogs

The effects of intravenous infusions of morphine, met-enkephalin and leu-enkephalin on gastric acid secretion, gastrin release and gastric emptying were investigated in four dogs with gastric cannulas stimulated by a liquid peptone meal. The actions of a potent opiate antagonist, naloxone, used alone or combined with opiates were also studied. Morphine, met-and leu-enkephalin decreased the fractional gastric emptying rate. Acid secretion was decreased by enkephalins and increased by high doses of morphine. Enkephalins and to a lesser degree morphine inhibited gastrin release during the first hour following the administration of the meal. Only leu-enkephalin decreases significantly the integrated gastrin response. Naloxone at the doses used antagonized partly or totally the effects of opiates on gastric emptying but not those on gastric secretion or gastrin release. Naloxone infused alone had no significant effect on the gastric functions tested. These studies indicate that in dogs stimulated by a liquid test meal, enkephalins inhibit gastric emptying, acid secretion and gastrin release. Morphine inhibits gastric emptying and gastrin release and enhances acid secretion.

Relationship of the Gastrin Response to the Amount of Food Ingested in Normal Subjects

The serum gastrin response to three different amounts of a same meal was studied in 8 normal subjects. The peak gastrin response was similar for the three meals, but the integarated gastrin response was larger with the largest meals. Comparison of the response to the two largest meals indicates that in a given subject the gastrin response is similar when test on different occasions. A good correlation was found between individual fasting concentrations of gastrin and peak gastrin levels after feeding but not between basal gastrin and integrated gastrin response. This could indicate that in normal subjects the first two parameters are primarily related to the same control mechanisms (possibly the G cell mass), while the integrated gastrin response reflects the effectiveness of the feedback mechanisms controlling gastrin release.

Effect of acute suppression of acid secretion by omeprazole on postprandial gastrin release in conscious dogs

The effect of acute suppression of acid secretion induced by administration of a single dose of omeprazole (2 mg/kg body wt) on postprandial gastrin release was studied in 10 conscious dogs. In omeprazole-treated dogs, a sustained gastrin release was observed during a 10-h period after feeding, although greater than 95% of the meal had left the stomach after 4 h. This sustained gastrin release could be inhibited by acidification of the gastric lumen, by somatostatin, and by atropine. Insulin and bombesin induced considerable gastrin release in omeprazole-treated dogs, but plasma gastrin concentrations returned almost to basal values after 3 h. Omeprazole administered alone had no significant effect on basal gastrin levels. These data indicate that, in dogs, when acid secretion is suppressed by omeprazole a meal induces a sustained gastrin release lasting for up to 10 h. This gastrin release is probably related to the fact that food has been in contact with the gastric lumen, as neither vagal nor bombesin stimulation induced such a sustained activity of the G cells.

Effect of cimetidine, ranitidine and omeprazole on postprandial gastrin and somatostatin release in conscious dogs

During a first series of experiments, the gastrin responses to a meal were measured and compared to the responses seen after administration of cimetidine (2.5 mg/kg/h) or omeprazole (2 mg/kg). During a second series of experiments the effects of cimetidine (2.5 mg/kg/h), ranitidine (0.5 mg/kg/h) and omeprazole (2 mg/kg) on post-prandial gastrin and somatostatin release were determined in experiments during which the intragastric pH was maintained close to 6.4. During a third series of experiments, the effects of cimetidine (2.5 mg/kg/h) and omeprazole (2 mg/kg) on basal gastrin and somatostatin release were estimated. Postprandial gastrin release was increased by cimetidine and by omeprazole. When acidification of the gastric content was prevented by intragastric titration, postprandial gastrin release was increased by about 100%. No further increase was observed when the animals were concomitantly treated with cimetidine, ranitidine or omeprazole. Intragastric titration did not alter postprandial somatostatin release. Concomitant administration of H2 blockers decreased the somatostatin response to the meal, while concomitant administration of omeprazole did not alter this release. No significant changes were observed in basal gastrin or somatostatin levels after administration of cimetidine or omeprazole.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of sham feeding on gastric emptying of liquids in dogs.

The effects of sham feeding and of cimetidine, an inhibitor of gastric acid secretion, used alone or in combination on the gastric emptying of liquids were studied in four dogs fitted with a gastric fistula and a Komarov esophagostomy. Gastric emptying of a 290-ml water meal was slowed by sham feeding but not by cimetidine. Our experiments indicate that, in dogs, sham feeding slows gastric emptying of liquids by a mechanism independent of the acid secretion induced by vagal stimulation.

Effect of jejunal resection on the gastric acid secretory response to pentagastrin, histamine and feeding in dogs.

In dogs with gastric fistulas and denervated pouches from the oxyntic area, the acid secretory responses to a meal and to graded doses of histamine and pentagastrin were measured before and after resection of the upper half of the small bowel. Intestinal resection caused a small but significant increase in submaximal and maximal response from the pouch to histamine and pentagastrin without modification of the ED50. This effect was not observed in the innervated stomach. The response from the pouch to feeding was markedly increased and prolonged. These data indicate that both an increase in stimulation and an increase of the response to this stimulation are responsible for the increased acid secretion observed in the pouch when resected dogs were fed. These effects could be explained by the withdrawal of inhibitors of intestinal origin.

Effect of insulin on acid and pepsin secretion in vagotomized and non-vagotomized patients already stimulated by pentagastrin

The effects of insulin on acid and pepsin secretion were studied in 16 non-vagotomized patients and 14 completely vagotomized patients, during the continuous intravenous infusion of pentagastrin (‘Peptavlon ICI’). In non-vagotomized patients, insulin did not alter the acid response to pentagastrin, whereas it strongly stimulated pepsin secretion. In contrast, insulin inhibited acid and pepsin secretion in vagotomized patients. The data presented suggest that after vagotomy, the inhibitory effect of insulin on acid secretion may determine the pattern of acid response during an insulin test.

Physiology of the Secretion of Acid, Pepsin, Sulfated Polysaccharides and Glycoproteins by the Dog Fundic Mucosa

The secretion of acid, pepsin, chondroitin sulfate and glycoproteins from mucus have been studied in four Heidenhain pouch dogs, under basal condition and during stimulation with histamine, a gastrin-