Basal Serum Gastrin Concentrations Research Articles

Fasting and food-stimulated serum gastrin concentration in 151 duodenal ulcer patients and 41 non-dyspeptic volunteers. Significant sex differences.

In 41 non-dyspeptic volunteers (18 females and 23 males) the fasting and food-stimulated serum gastrin concentration was investigated. No significant sex differences were found in the basal serum gastrin concentration. The integrated postprandial gastrin output, however, was significantly higher in females than in males. In 151 duodenal ulcer patients (31 women and 120 men) significant sex differences were found in both the fasting and the food-stimulated serum gastrin concentration. Women had values approximately 60% higher than men. In 116 of the patients (27 women and 89 men) the basal and pentagastrin-stimulated gastric acid concentrations were investigated. In the basal state no significant sex differences in acid output were found. After stimulation women had significantly lower gastric acidity and gastric acid output than men.

Effect of omeprazole on gastric acid secretion in man.

Omeprazole in doses of 20, 40 or 60 mg dose-dependently inhibits basal acid secretion in young healthy subjects, with almost complete inhibition by 60 mg. Omeprazole has also been shown to dose-dependently inhibit vagally stimulated and meal stimulated acid secretion. Pentagastrin stimulated acid secretion is strongly inhibited by omeprazole for 4-5 hours, with moderate inhibition remaining 24 hours after a single dose. The plasma half-life of omeprazole, however, is about 50 minutes. The inhibitory effect accumulates over the first few days of repeated administration, and the effect continues for at least 24 hours after the last dose. A relatively high dose of intravenous omeprazole is required to keep the gastric pH above 4 over the 24-hour period. Both basal and postprandial serum gastrin concentrations have been observed to increase during omeprazole treatment. These changes, however, are probably secondary to a pronounced reduction of intragastric acidity which relieves acid inhibition of gastrin release from the antrum.

Effects of portacaval shunt on the rat stomach

In portacaval-shunted rats, basal but not pentagastrin-stimulated acid secretion was higher than in sham-operated controls. The basal serum gastrin concentration was unchanged and the postprandial serum gastrin concentration lowered following portacaval shunt. Thus, gastrin is not responsible for the elevated basal acid secretion. The present study provides evidence that there is no trophic effect on the oxyntic mucosa as a whole and that there is no change in parietal cell-associated gastrin receptors after portacaval shunting. Interestingly, however, endocrine cells in the oxyntic mucosa (the histamine-containing ECL cells) proliferated greatly and the pentagastrin- and cholecystokinin octapeptide-induced activation of the histamine-forming enzyme, histidine decarboxylase, in these cells was much greater than in control rats. Analysis of the dose-response curves for the enzyme-activating effect of pentagastrin and cholecystokinin-octapeptide indicated that the D50 values for these two stimulants were not altered by shunting but that the maximal enzyme activation was greatly elevated. The enhanced enzyme activation can be partly, but not fully, explained by the fact that the ECL cells were increased in number. The enhanced response following portacaval shunt probably reflects also an increased number of gastrin receptors per ECL cell. The effect of portacaval shunting on gastric ECL cells can perhaps be explained by impaired degradation in the liver of intestinal substance(s) exerting a highly specific trophic effect on the ECL cells or, alternatively, causing an enrichment of gastrin receptors on these cells, thereby making them more sensitive to the trophic effect of gastrin. The ECL cell hyperplasia is manifest about 4 weeks after the shunting. A modified procedure for portacaval shunting which left the gastroduodenal vein (otherwise ligated) drained to the liver produced the same trophic effect as conventional portacaval shunt, suggesting an intestinal rather than gastroduodenal origin of the agent(s) responsible for the trophic action.

Effect of indomethacin on gastric acid and bicarbonate secretion in humans

The role of endogenous prostaglandins in the physiologic regulation of gastric secretion is unclear. We evaluated the effect of indomethacin, an inhibitor of endogenous prostaglandin synthesis, on basal gastric secretion in humans using a two-component model for calculating gastric acid and bicarbonate secretion. After a control, gastric secretory study, 11 healthy volunteers were given 50 mg of indomethacin orally every 8 h for a total of 10 doses, after which the gastric secretory experiment was repeated. Indomethacin significantly (p < 0.05) increased basal gastric juice volume, hydrogen ion concentration, osmolality, and acid output. Indomethacin increased acid secretion significantly (from 4.9 ± 1.2 to 7.4 ± 1.7 mmol/75 min, p < 0.02) without affecting gastric bicarbonate secretion (control 2.7 ± 0.8, indomethacin 3.0 ± 0.7 mmol/75 min; p > 0.05). The increase in basal acid secretion after indomethacin administration was quite variable from subject to subject and was unaccompanied by significant changes in basal serum gastrin concentrations. Unlike basal acid secretion, indomethacin had no significant effect on acid secretion stimulated by intragastric infusion of homogenized food. Moreover, indomethacin did not prevent intravenous somatostatin 14 from inhibiting food-stimulated acid secretion, in contrast to a previous study in rats in which indomethacin blocked the inhibitory effect of somatostatin on acid secretion. Assuming the effect of indomethacin is due to reduced endogenous prostaglandin synthesis, we conclude that (a) in some individuals endogenous prostaglandins suppress basal acid secretion by a mechanism independent of the hormone gastrin; (b) endogenous prostaglandins play little, if any, role in the regulation of basal bicarbonate secretion by the stomach; and (c) endogenous prostaglandins do not regulate food-stimulated acid secretion, nor do they mediate the inhibitory effect of somatostatin on gastric acid secretion in humans.

The Type of Anastomosis after Selective Gastric Vagotomy and Precise Antrectomy Is of No Importance for Basal and Postprandial Serum Gastrin Concentration

Twenty-six patients were treated for duodenal or recurrent ulcer with selective gastric vagotomy plus precise antrectomy--that is, complete removal of the entire antrum. Sixteen had a gastroduodenal anastomosis and 10 a gastrojejunal anastomosis. Fasting and protein meal-stimulated serum gastrin concentration was measured in 10 patients before antrectomy and in all after the operation. Fasting serum gastrin concentration was reduced and food-stimulated gastrin response abolished irrespective of the type of the anastomosis. It is concluded that a postprandial gastrin rise means retained antral tissue in the gastric remnant and that neither protein nor mechanical stimulation of the passage of food through the duodenum stimulates the duodenal G-cells to gastrin release.

Sex-related differences in gastrin release and parietal cell sensitivity to gastrin in healthy human beings.

We compared serum gastrin concentrations and gastric acid secretion basally and in response to a mixed meal in age-matched women and men. Women had significantly higher basal serum gastrin concentrations (P < 0.01) and two- to threefold higher food-stimulated serum gastrin concentrations (P < 0.001) than men. Basal and food-stimulated serum gastrin concentrations in women did not fluctuate significantly during the menstrual cycle. Sex-related differences in food-stimulated serum gastrin concentrations were not due to differences in antral pH because pH after the meal in women and men had been kept constant at 5.0 by in vivo intragastric titration with sodium bicarbonate. Studies using an antibody that reacts only with potent gastrin heptadecapeptide species (G-17-I and II) indicated that women also had threefold higher serum G-17 concentrations after the meal than men (P < 0.005). Elevated serum G-17 concentrations after the meal in women were due to increased release of G-17 rather than slower clearance of G-17 from the circulation.Despite elevated serum gastrin concentrations in response to food, women secreted approximately the same amount of acid relative to their maximal secretory capacity as men. Furthermore, during exogenous G-17 infusion, which led to identical serum gastrin concentrations in women and men, the dose-response curve for acid secretion in women was shifted significantly to the right of the G-17 dose-response curve in men (P < 0.02). The dose of G-17 that stimulated half of peak acid secretion was two to three times higher in women than in men, reflecting significantly reduced sensitivity of parietal cells to gastrin in women (P < 0.05). Our studies suggest that, compared with men, women release greater amounts of gastrin but are at the same time less sensitive to stimulation of acid secretion by gastrin.

Effect of bethanechol on gastric acid secretion and serum gastrin concentration after proximal gastric vagotomy.

It has been suggested that maximal acid output decreases after vagotomy as a result of reduced cholinergic activity and that maximal acid secretion can be restored to prevagotomy levels with cholinergic agonists. To test this, a maximally tolerated dose of bethanechol (50 micrograms/kg/hr) or saline was infused intravenously in nine duodenal ulcer patients who had been treated by proximal gastric vagotomy. Bethanechol infusion significantly (p less than 0.05) increased basal acid secretion without affecting basal serum gastrin concentrations. Despite stimulation of basal acid secretion, bethanechol had no significant effect on maximal acid output in response to subcutaneous pentagastrin. Although bethanechol significantly increased maximal acid output in response to subcutaneous histamine, maximal acid secretion in response to histamine (or to pentagastrin) was not restored to the prevagotomy level in any patient. Thus, factors other than loss of cholinergic activity appear to be responsible for the large reduction in maximal secretory capacity after vagotomy.

Basal serum gastrin concentration related to complications, blood groups, and season in duodenal ulcer.

In 229 consecutive duodenal ulcer patients basal serum gastrin concentration was examined in relation to ulcer complications, ABO blood groups, and seasons and was found to be independent of these factors.

EFFECTS OF FM100, A FRACTION OF LICORICE ROOT, ON SERUM GASTRIN CONCENTRATION IN RATS AND DOGS

The effects of FM100, a fraction of licorice root with antiulcer activity, on serum gastrin concentration were investigated in rats and dogs. The basal serum gastrin concentration in conscious rats was not affected by 400 mg/kg, p.o. of FM100, but was increased by 800 mg/kg. p.o. of FM100. The serum gastrin concentration of rats, in which the antrum had been separated from the fundus was decreased by intraduodenal administration of FH100 in a dose-dependent manner. In conscious beagles, the increase in serum gastrin concentration induced by feeding was not affected by pretreatment with 400 mg/kg p.o. of FM100. However, in anesthetized dogs in which the antrum had been separated from the fundus, the increase in acid output and serum gastrin concentration after administration of peptone solution was prevented by the intraduodenal administration of 200 mg/kg of FM100. These results suggest that the gastric anti-secretory action of FM100 may be due to the inhibition of endogenous gastrin release.

Effects of FM100, a fraction of licorice root, on serum gastrin concentration in rats and dogs.

The effects of FM100, a fraction of licorice root with antiulcer activity, on serum gastrin concentration were investigated in rats and dogs. The basal serum gastrin concentration in conscious rats was not affected by 400 mg/kg. p.o. of FM100, but was increased by 800 mg/kg, p.o. of FM100. The serum gastrin concentration of rats in which the antrum had been separated from the fundus was decreased by intraduodenal administration of FM100 in a dose-dependent manner. In conscious beagles, the increase in serum gastrin concentration induced by feeding was not affected by pretreatment with 400 mg/kg p.o. of FM100. However, in anesthetized dogs in which the antrum had been separated from the fundus, the increase in acid output and serum gastrin concentration after administration of peptone solution was prevented by the intraduodenal administration of 200 mg/kg of FM100. These results suggest that the gastric anti-secretory action of FM100 may be due to the inhibition of endogenous gastrin release.

The relation between basal gastric pH and serum gastrin.

In a normal middle-aged population the basal serum gastrin concentration and gastric pH were determined. Persons with achlorhydria were excluded. In 550 nonachlorhydric persons the relation between ba

Depressed gastrin secretion in burns

In 5 burned subjects we investigated basal serum gastrin concentration and serum gastrin responses to a meal in the acute phase and after the healing ofburns. We found serum gastrin responses during the acute phase to be 62 per cent of the values observed after healing. This difference is significant (P < 0−025), whereas there was no difference in basal concentrations of gastrin in serum. The findings do not support the theory that stress ulcers are related to hypergastrinaemia.

Serum gastrin in patients with chronic renal failure.

The realisation that circulating gastrin is heterogeneous necessitates a reappraisal of gastrin's role in the increased incidence of duodenal ulcer disease that occurs in chronic renal failure. Radioimmunoassays employing region-specific antisera have been used to examine renal and extrarenal factors controlling serum gastrin concentration in patients with chronic renal failure. The present study has shown that basal serum gastrin concentrations measured with a carboxyl-terminal specific antibody were significantly higher in eight patients with chronic renal failure treated by dietary restriction (388+/-196 pM) than in 14 patients with chronic renal failure treated by haemodialysis (28.7+/-4.6 pM). However, basal gastrin concentrations in both groups of patients were significantly higher than in 25 normal subjects (12.3+/-1.8 pM) and showed significant negative correlations with maximal gastric acid secretion (p < 0.01). Markedly raised basal gastrin concentrations were observed only in chronic renal failure patients who were also achlorhydric. Although the peak postprandial increment in big gastrin concentration in 11 chronic renal failure patients (34.0+/-7.5 pM) was significantly greater (p < 0.05) than in 25 normal subjects (19.5+/-4.6 pM), the little gastrin responses were not significantly different. In addition, clearance of exogenous little gastrin was similar in four chronic failure patients (clearance half time: 8.1+/-0.7 min) and four normal subjects (clearance half time: 6.5+/-1.2 min). These studies suggest that the human kidney is unimportant in the metabolism of little gastrin. As circulating little gastrin is six times more potent than big gastrin in stimulating acid secretion, these studies suggest that the raised gastrin concentrations observed in patients with chronic renal failure have little significance in terms of their increased incidence of duodenal ulcer disease.

Relationship Between Basal Serum Gastrin Concentrations and Gastric Acid Secretion in Peptic Ulcer Disease

In large groups of control subjects and gastric, prepyloric, and duodenal ulcer patients basal gastrin concentration as basal and maximal acid output was measured. All groups had equal basal gastrin concentrations, except gastric ulcer patients, who had higher values (p less than 0.001). A significant negative correlation was found between acid output and basal gastrin in controls and prepyloric ulcer patients. In duodenal ulcer a similar correlation was seen only after exclusion of gastrin and basal acid hypersecretors, and in gastric ulcer no correlation could be found. The characteristic pattern for gastrin and acid secretion was in prepyloric ulcer patients almost like that in controls, whereas gastric ulcer patients seemed more heterogeneous. In duodenal ulcer differences may be explained by a defective feedback inhibition of acid.

Effect of sham feeding on gastric acid secretion in healthy subjects and duodenal ulcer patients: Evidence for increased basal vagal tone in some ulcer patients

Sham feeding augments gastric acid secretion by activating efferent vagal pathways to the stomach. If increased vagal activity in the basal state were the cause of increased basal acid secretion in some patients with duodenal ulcer, these patients might be expected to secrete little or no additional acid in response to sham feeding. To test this, we measured basal and sham feeding-stimulated acid secretion (as well as peak pentagastrin-stimulated acid output) in 29 duodenal ulcer patients and 22 healthy subjects. Four ulcer patients who had markedly increased basal acid secretion (basal/peak acid output > 0.30) and normal basal serum gastrin concentrations failed to augment acid secretion in response to sham feeding. On the other hand, patients with marked basal acid hypersection owing to hypergastrinemia (Zollinger-Ellison syndrome) responded to sham feeding with a large increase in acid secretion above basal rates. Every normal subject responded to sham feeding with an increase in acid secretion above basal rates, even when acid secretion had been stimulated by an intravenous pentagastrin infusion before beginning sham feeding. These findings suggest that in some patients with duodenal ulcer (4 of 29 in this study) increased basal acid secretion is caused by increased vagal tone.

The effect of renal transplantation on basal serum gastrin concentration.

Basal serum gastrin concentration was measured before and every week during the initial 5 weeks after renal transplantation in 9 of 20 patients with chronic renal failure who obtained a well functioning renal transplant. Furthermore, calcium and phosphorus metabolism in relation to serum gastrin was investigated in all 20 patients 5 weeks after transplantation. Before renal transplantation, serum gastrin was markedly elevated as compared with the levels in normal controls. During the first 3-5 weeks after renal transplantation, serum gastrin decreased towards normal values. A slight but significant increase in serum gastrin persisted 5 weeks after transplantation. No significant relation between changes in serum gastrin concentration and in calcium and phosphorus metabolism was observed.

Fasting and postprandial serum gastrin in neonatal swine, and changes following antrectomy

Understanding of the physiology of the gastrointestinal hormone gastrin in the adult individual has advanced rapidly in recent years, but comparable information is lacking for the neonate. Serum gastrin concentrations were studied in 16 neonatal piglets in the basal and postprandial state. In piglets less than 2 weeks of age, the mean basal serum gastrin concentration was 85.04 pg/ml. No significant postprandial elevations were noted at 15 and 45 min following a high protein meal. In piglets between 2 and 4 weeks of age, the mean basal concentration was 123.58 pg/ml and, again, no significant postprandial elevations were noted. Antrectomy in animals between 2 and 4 weeks of age resulted in marked decrease in serum gastrin concentrations with no response to instillation of protein solutions into the duodenum. Comparison of these experimental studies with clinical studies in normal human neonates reported from our institution suggests that the neonatal swine may provide a suitable experimental model for study of gastrin homeostasis in the neonate.

The influence of an abnormal duodenal loop on basal and food-stimulated serum gastrin concentrations.

Postprandial serum gastrin secretion was studied in 26 patients with X-ray-negative dyspepsia. Seven patients had a normal duodenum while 19 had duodenal anomalies. In patients with an abnormal duodenal loop, the mean postprandial serum gastrin secretion was significantly higher after 45, 60 and 120 min than that of the control group. No significant difference was demonstrated in the basal state. A delay in gastric emptying rate might be the cause of increased postprandial serum gastrin secretion in patients with an abnormal duodenal loop.

Effect of Secretin on Gastric Function in Normal Subjects and in Patients with Duodenal Ulcer

The effect of constant intravenous infusion of secretin in doses of 0.25, 0.50, 1.50, and 3.0 mug per kg per hr on meal-stimulated acid secretion was measured in vitro titration to pH 5.0. The pattern and degree of secretin inhibition of food-stimulated acid secretion depended on when the secretin infusion was begun, the effect being more pronounced when the secretin was begun 1 hr before the test meal than when the meal and secretin infusions were begun simultaneously. Inhibition of acid secretion in normals was approximately the same as in 2 patients with pancreatic exocrine insufficiency who could secrete only small amounts of pancreatic bicarbonate in response to secretin. Secretin in dose of 0.25 and 0.5 mug per kg per hr inhibited acid secretion only slightly, whereas 3.0 mug per kg per hr completely stopped acid secretion. Inhibition of acid secretion by secretin was similar in controls and in patients with duodenal ulcer. Secretin also reduced the rise in serum gastrin concentration after the meal, and delayed gastric emptying; both responses were approximately the same in normals and in duodenal ulcer patients. Secretin inhibited basal gastric acid secretion but had no consistent effect on basal serum gastrin concentration.

The relation between functioning parietal cell and gastrin cell masses in two groups of duodenal ulcer patients.

1. Serum gastrin concentrations before and after a standardized meal were determined in twenty-eight patients with duodenal ulcer and in ten normal control subjects. 2. In response to pentagastrin, thirteen of the duodenal ulcer subjects secreted acid within the limits of normal and fifteen secreted in excess. 3. The differences in the basal serum gastrin concentrations between the three groups, normal subjects, acid "normosecretors" and hypersecretors were not statistically significant but that of the hypersecretors was suggestively low. 4. The integrated gastrin response and peak gastrin responses to meals were higher in duodenal ulcer patients with normal acid secretion than in the hyper-secretors but the values for the latter were not different from normal subjects. 5. Stabilization of intragastric pH by infusion into the antrum of sodium bicarbonate during the test meal response period did not alter these differences between the two ulcer patient groups. 6. A significant inverse correlation exists between the maximal acid output and the integrated gastrin response in both normal subjects and hypersecreting duodenal ulcer patients. 7. The evidence (a) supports the existence of an inverse relationship between the functioning parietal cell and gastrin cell masses, (b) shows the gastrin response in normosecreting ulcer subjects to be inappropriately high, and (c) suggests that excessive vagotonia exerts trophic effects upon both parietal cell mass and gastrin cell mass.