Woussen-Colle Mc

Influence of the stimulation state of the parietal cells on the inhibitory effect of omeprazole on gastric acid secretion in dogs

Abstract The relationship between the stimulation state of the parietal cells and the gastric antisecretory properties of omeprazole has been evaluated in dogs with gastric fistulas maximally stimulated with pentagastrin. Intravenous administration of omeprazole (5 μmol/kg) 4 h before the start of stimulation with pentagastrin inhibited the acid response by 71%. This inhibition was prevented when omeprazole was given during an infusion of somatostatin at a dose that completely inhibited acid secretion. When given 18 h before stimulation with pentagastrin, omeprazole inhibited the acid response by 50%. This inhibitory effect was almost completely suppressed when omeprazole was administered during an infusion of somatostatin or after the administration of cimetidine, and was increased when omeprazole was given during an infusion of pentagastrin. These data indicate that the inhibitory effect of omeprazole given by rapid intravenous injection is related to the activity of the parietal cells at the moment of administration of the drug. They suggest that, in the intact animal as well as in the isolated gastric glands, the uptake of omeprazole by the parietal cells is related to the stimulation state of these cells.

The activation of adenylate cyclase by pituitary adenylate cyclase activating polypeptide (PACAP) via helodermin-preferring VIP receptors in human SUP-T1 lymphoblastic membranes

Competition binding curves, using [125I-acetyl-His1]PACAP-27 as radioligand and dose-effect curves of adenylate cyclase activation in human SUP-T1 lymphoblastic membranes showed that PACAP-27 and PACAP-38 stimulate the enzyme through a single class of helodermin-preferring VIP receptors with the following order of potency: helodermin = [acetyl-His1]PACAP-27 greater than PACAP-38 greater than PACAP-27 greater than VIP. PACAP (6-27) (Ki 0.5-0.8 microM) and [Des-His1, Asn3]PACAP-27 (Ki 1-2 microM) acted as competitive antagonists. Using a series of 13 PACAP-27 analogues and fragments and three VIP analogues, we identified positions 1, 2, 3, 9 and 13 in PACAP-27 as being of importance for high-affinity binding. Thus, we added further evidence for considering that the present helodermin-preferring VIP receptors, when compared to a majority of VIP receptors and PACAP receptors, exhibit an original specificity pattern.

Antral Gastrin Cell Hyperplasia in Patients with Peptic Ulcer

The total number of gastrin (G) cells in the stomach was determined by using a histologic counting method and planimetry in ulcerous and nonulcerous patients. The preoperative basal and postprandial serum gastrin values and the gastrin cell mass in the gastrectomy specimen could be compared in 16 surgical patients. There was a significant correlation between the integrated gastrin response to feeding and the total gastrin cell number in the stomach. No correlation was found between the basal serum gastrin level and the total gastrin cell count. A total gastrin cell number higher than 50 million was found in the stomach of three duodenal ulcer patients with preoperative postprandial hypergastrinemia as well as in one patient with normal scrum gastrin values. Gastrin cell counts between 6 and 42 million were found in control stomachs and in patients with gastric ulcer. Preoperative feeding tests could be useful to select patients with an elevated antral G cell number.

Presence of helodermin-like peptides of the VIP-secretin family in mammalian salivary glands and saliva

Helodermin is a biologically active peptide isolated from the venom of the Gila monster lizard (Heloderma suspectum) whose structure is related to that of vasoactive intestinal peptide and secretin. Using a specific radioimmunoassay based on antisera prepared by immunizing rabbits with natural helodermin, we demonstrated the presence of helodermin‐like material in mammalian salivary glands, including parotid, submaxillary and sublingual glands from rat and dog, and parotid and submaxillary glands from man. All helodermin‐like materials had an apparent molecular mass of 4–12 kDa. Dog saliva, collected after pilocarpine stimulation, revealed similar immunoreactivity with a major component around 6 kDa.

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 vagotomy and atropine on plasma somatostatin response to a meal in conscious dogs

In 4 conscious dogs with gastric fistulas the somatostatin responses to a meal were measured and compared to the responses seen after i.v. infusion of atropine sulfate (20 and 50 micrograms.kg-1.h-1) or cimetidine (8 mg.kg-1.h-1). The experiments were repeated after truncal vagotomy. The somatostatin responses to bombesin (0.5 micrograms.kg-1.h-1) were also measured before and after vagotomy. Vagotomy decreased basal and postprandial somatostatin levels and reduced the somatostatin responses to feeding during the first 30-min period following the ingestion of the meal but not during subsequent periods. Bombesin-induced somatostatin release was increased after vagotomy. Atropine decreased the somatostatin responses to the meal before and after vagotomy. Cimetidine had no significant effect. These studies suggest that, in conscious dogs, somatostatin released into the circulation is partly under vagal control and that, as for gastrin release, vagal pathways for stimulation and inhibition are present. Our studies also suggest that cholinergic mechanisms are involved in the control of postprandial somatostatin release.

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.