Gastrin Release In Man Research Articles

Effect of Parietal Cell Vagotomy and Cholinergic Blockade on Gastrin Release in Man Induced by Gastrin-Releasing Peptide

The influence of cholinergic blockade as well as vagal denervation of the oxyntic gland mucosa on the gastrin response to gastrin-releasing peptide (GRP) have been studied in patients with duodenal ulcer disease. The gastric luminal content was neutralized during the experiments. GRP induced a substantial increase in gastrin levels with a peak response already after 15 min of infusion. Vagal denervation of the parietal cell area induced a significant increase in basal gastrin concentrations and a significant enhancement of the GRP response. Two different doses of benzilonium bromide were studied and neither influenced the basal concentrations of gastrin. A significantly increased gastrin response to GRP was, however, observed after administration of both a high and a very low dose of the anticholinergic drug. Our results delineate a vagal, noncholinergic inhibitory influence on the basal gastrin release. In addition a vagally dependent oxyntopyloric mechanism inhibits the gastrin release stimulated by GRP. This inhibitory mechanism may hypothetically be a cholinergic reflex mechanism.

Tolbutamide inhibits gastrin release in man.

Tolbutamide significantly decreased fasting plasma gastrin after 5 min of intravenous infusion in patients with atrophic gastritis, duodenal ulcer, or insulin-dependent diabetes mellitus (IDDM) as well as in healthy volunteers. Increased plasma insulin and decreased blood glucose were observed in patients with atrophic gastritis, duodenal ulcer and healthy volunteers, but not in patients with IDDM. Suppression of plasma gastrin in healthy volunteers was also observed following oral administration of tolbutamide. Despite the observed decrease in plasma gastrin, neither basal nor tetragastrin-stimulated acid output was changed for 30 min following tolbutamide infusion in healthy volunteers. Thus, our data suggest that tolbutamide inhibits gastrin release in man via mechanisms independent of changes in plasma insulin, blood glucose or acid secretion.

Effect of histamine H2-receptor stimulation on bombesin- and peptone-stimulated gastrin release in man.

This study was undertaken to determine whether histamine H2-receptors are involved in the regulation of gastrin secretion in man. Since previous studies on the effect of histamine H2-receptor blockade on gastrin release are conflicting, we have studied the effect of histamine infusion (130 nmol/kg/hr) with simultaneous H1-receptor blockade on gastrin release in healthy male subjects. Intragastric pH was maintained at 4.5 by continuous intragastric titration during all studies. Histamine did not affect gastrin release stimulated by infusion of bombesin (90 pmol/kg/hr) or by a peptone meal. Integrated gastrin secretion during bombesin plus histamine was 767 +/- 151 pmol X min/liter (+/- SEM), compared to 757 +/- 144 pmol X min/liter during bombesin plus saline (not significant), whereas integrated meal-stimulated gastrin release was 1666 +/- 456 pmol X min/liter during histamine and 1856 +/- 492 pmol X min/liter during saline. It is concluded that histamine H2-receptors do not seem to be involved in the regulation of gastrin secretion in man.

Influence of caloric intake on gastric inhibitory polypeptide, VIP and gastrin release in man

Blood glucose, gastric inhibitory polypeptide (GIP), vasoactive intestinal polypeptide (VIP) and gastrin secretions were measured over a three-hour period following the ingestion by normal subjects of a mixed meal with two different caloric levels (1055 Kcal and 1192 Kcal). No VIP secretion was observed after either meal. Gastrin release was not modified by the increase of caloric intake (mainly carbohydrates and lipids), whereas GIP secretion was significantly more important after the meal with the highest caloric value (peak at 30 mn: 499.5±250.4 vs. 273.4±128.7 pg/ml and integrated response 53.3±20.5 vs. 28.2±9.9 ng× ml −1×180 min −1−p<0.05 ). This difference could not be attributed to glucose since the blood glucose levels were not significantly different. It is more probably related to the total amount of ingested food. This suggests the existence of rapid mechanisms of adaptation to the incoming load of the GIP-producing cells.

Fasting and food-stimulated plasma gastrin levels in chronic Chagas' disease.

Chagas' disease is known to be associated with extensive lesions of the intramural neurons of the digestive tract. In order to evaluate the contribution of the intramural plexuses to the control of plasma gastrin levels in man, we performed the following measurements: (a) fasting plasma gastrin in 18 chagasic patients and 16 control subjects; (b) integrated gastrin response to food in 9 chagasic patients and 10 controls, (c) basal acid secretion and gastric acid responses to graded doses of pentagastrin in 14 chagasic and 13 controls. Fasting plasma gastrin levels and integrated gastrin response were significantly higher in chagasics than in controls. Basal and maximal acid secretion and responsiveness of acid-secreting gastric cells were lower in chagasics. These results indicate that the intramural plexuses play a role in the control of gastrin release in man.

Effect of dopamine infusion on gastric and pancreatic secretion and on gastrin release in man.

The effect of dopamine infusion on basal and pentagastrin-stimulated gastric secretion, on basal and secretin-CCK-PZ-stimulated pancreatic secretion, and on basal and meal-induced gastrin release has been evaluated in healthy volunteers. Both basal and stimulated gastric acid secretion were significantly inhibited during dopamine infusion with a significant rebound to pre-infusion values after discontinuing dopamine. These effects were prevented by pretreatment with the antidopaminergic drug, metoclopramide. A slight but now significant decrease in amylase and bicarbonate outputs was also observed during dopamine infusion, while gastrin release did not change. These data suggest the existence of dopaminergic mechanisms in the regulation of gastric acid secretion in man.

The Effect of Mucaine on Gastrin Release in Man

The effect of Mucaine and Aludrox on basal and food stimulated immunoreactive gastrin has been assessed in normal control subjects and patients with duodenal or gastric ulcer. No differences in gastrin responses were observed either in the basal period or after the protein meal with the two antacids. As previously described, release of gastrin was greatest in gastric ulcer patients but in contrast to previous results,normal subjects seemed to show a greater response than duodenal ulcer patients but this was not statistically significant. Thus the combination of a local anaesthetic oxethazaine with aluminium hydroxide gel does not lead to diminished gastrin release and is not the prime mechanism of action of this agent.

The Effect of Mucaine on Gastrin Release in Man

Summary: The effect of Mucaine and Aludrox on basal and food stimulated immunoreactive gastrin has been assessed in normal control subjects and patients with duodenal or gastric ulcer. No differences in gastrin responses were observed either in the basal period or after the protein meal with the two antacids. As previously described, release of gastrin was greatest in gastric ulcer patients but in contrast to previous results, normal subjects seemed to show a greater response than duodenal ulcer patients but this was not statistically significant. Thus the combination of a local anaesthetic oxethazaine with aluminium hydroxide gel does not lead to diminished gastrin re/ease and is not the prime mechanism of action of this agent.

Gastric luminal gastrin release in man: Effects of calcium and pH

Gastric luminal gastrin release in man: Effects of calcium and pH

Is there an Oxyntopyloric Reflex for Release of Gastrin in Man?

Plasma gastrin concentrations and gastric acid output were measured during graded balloon distention of the gastric fundus and body in 20 patients with duodenal ulcer. Acid output rose stepwise with increasing distention volumes but plasma gastrin remained unchanged. During intragastric neutralization in 5 of these subjects, fundic distention did not elicit a significant rise in plasma gastrin, whereas the acid response was similar to that observed in the control study when the gastric contents were acid. In 8 of the 20 patients, proximal gastric vagotomy profoundly suppressed the acid response to fundic distention. Basal plasma gastrin concentrations were elevated after vagotomy but were unchanged during graded fundic distention. The results suggest that neural reflex activation of the oxyntic glands is the main mechanism by which fundic distention stimulates acid secretion in man. The failure of fundic distention to release gastrin does not, however, completely rule out the existence of an oxyntopyloric distention reflex for gastrin release in man. Fundic distention in man seems to both stimulate acid secretion and induce an inhibitory mechanism acting on acid secretion. This inhibitory mechanism may, purely speculatively, also mask the effect of an oxyntopyloric reflex for gastrin release. The present study and earlier work suggest that in man distention of the stomach is a poor stimulus for release of gastrin, regardless of whether the pyloric or the oxyntic gland area, or both, are distended.

Lack of Caffeine Stimulation of Gastrin Release in Man

Summary and conclusionsCaffeine ben-zoate given intravenously to four subjects (two with duodenal ulcer and two normals) in dose-responsive tests at 80 and 320 mg/hr stimulated gastric H+ and pepsin secretion two- and threefold, respectively, but did not change serum gastrin levels. In five patients with duodenal ulcer and six normals, 250 mg of caffeine benzoate intragastrically, but not an equivalent volume of water, raised serum gastrin concentrations by 16 to 22 pg/ ml (P < 0.05). There was no difference in caffeine-stimulated gastrin release between the duodenal ulcer group and normals.

Effects of somatostatin on gastric secretion and gastrin release in man.

Somatostatin, a recently synthesized hypothalamic growth hormone release-inhibiting factor (GIF), was used in the cyclic and linear form. In all subjects studied, the cyclic GIF inhibited gastrin secretion during basal conditions as well as during a standard food stimulus, with immediate rebound after the infusion was stopped. Similar responses were observed in a hypophysectomized patient, indicating that this effect of GIF was independent of suppression of growth hormone secretion. Cyclic and linear GIF, when administered in normal subjects during an infusion of synthetic human gastrin I, almost totally suppressed gastric secretion. The results indicate that GIF is a potent inhibitor of gastric secretion and gastrin release.