gastrin-17 and Duodenal-Ulcer

In contrast to healthy subjects, duodenal ulcer patients in the active phase contain large amounts of a peptide in serum and antrum which react with antiserum specific for the N-terminus, but not the C-terminus of gastrin-17. The immunochemical and chromatographic properties were similar to that of the N-terminal tridecapeptide sequence of gastrin-17. The peptide follows the clinical course of duodenal ulcer disease, as it disappears when the ulcer heals. The N-terminal tridecapeptide - lacking the bioactive tetrapeptide of gastrin-17 - is a potent inhibitor of gastric acid secretion, presumably by way of competitive antagonism to gastrin. It is suggested to participate in the regulation of gastric acid secretion in patients with active duodenal ulcer disease. To confirm the chemical structure of the peptide, antral and gastrinoma extracts were used for isolation, purification and amino acid analysis. We found two different peptides with the same N-terminus as gastrin-17, namely the previously known N-terminal tridecapeptide fragment of gastrin-17 and a new gastrin component, identical with a C-terminal glycine extended gastrin-17. Furthermore, a C-terminal glycine extended component, corresponding to each of the other molecular forms of gastrin were present. Thus, a variety of abnormally processed gastrins are synthesized and released to the circulation during the active period of duodenal ulcer disease.

Topics: Amino Acid Sequence; Animals; Chemical Phenomena; Chemistry; Duodenal Ulcer; Gastrins; Humans; Species Specificity; Terminology as Topic; Tissue Extracts

The aim of this study was to assess the gastric histopathology and serum gastrin-17 and pepsinogens profiles in patients with duodenal ulcer before and after Helicobacter pylori eradication in a population with a very high prevalence of H. pylori. At the same time we assessed the role of H. pylori density on these variables.. Eighty Caucasian patients with H. pylori-associated duodenal ulcer before treatment and 1 year after randomized eradication were studied. Among patients with unsuccessful eradication two groups were distinguished according to the data obtained after treatment: the group with negative rapid urease test and decreased bacterial density according to morphological score (partial elimination group); the group with positive rapid urease test and high bacterial density (failed eradication group).. One year after successful eradication, serum levels of gastrin-17, pepsinogen I and pepsinogen II decreased. Similar changes of serum pepsinogen I and pepsinogen II levels were observed in patients with partial elimination of H. pylori infection. In the group with successful eradication, inflammation, activity, atrophy and number of lymphoid follicles in the antral mucosa fell. In the group with partial elimination, antral mucosa activity and H. pylori score reduced. Other morphological changes were statistically non-significant.. Patients with duodenal ulcer after successful eradication have improvement of morphological and functional characteristics of gastric mucosa.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Antibodies, Bacterial; Biomarkers; Down-Regulation; Drug Therapy, Combination; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Proton Pump Inhibitors; Time Factors; Treatment Failure; Treatment Outcome; Urease; Young Adult

The article discloses the results of the duodenal ulcer treatment with a generic of omeprazole (Omizac) in the in-patient hospital and polyclinic conditions, dynamics of the serum gastrin level against the background of the drug application and after its withdrawal, and assessment of the intensity and duration of acid production inhibition in the stomach.

Topics: Adult; Anti-Ulcer Agents; Biomarkers; Dose-Response Relationship, Drug; Drug Administration Schedule; Duodenal Ulcer; Female; Gastrins; Humans; Male; Omeprazole; Treatment Outcome

to study the specific features of working conditions in workers from the chemical plants manufacturing nitrogen compounds by the groups under study and by the time course of changes in the serum levels of gastrin-17 (G-17) and pepsinogen-1 (P-1) in relation to the chemical composition of noxious substances, the length of service, the stage of the disease, and the performed therapy.. A test GastroPanel was used to study the serum levels of G-17 and P-1 in 54 patients with duodenal peptic ulcer (DPU) who worked at the chemical plants manufacturing nitrogen compounds (a study group) and in 15 healthy individuals (a control group).. The objective data on the time course of changes in the functional characteristics (G-17 and P-1) of the gastric mucosa (GM) in patients with DPU vary with the chemical composition of noxious substances and the length of service in chemical industry. The basic therapy for PDU contributes to a positive change in the functional parameters reflecting the state of GM.. In patients with DPU, the working conditions at the chemical plants manufacturing nitrogen compounds result in changes in the functional parameters reflecting the state of GM

Topics: Adult; Biomarkers; Chemical Industry; Diagnostic Techniques, Digestive System; Duodenal Ulcer; Endoscopy, Gastrointestinal; Follow-Up Studies; Gastric Mucosa; Gastrins; Humans; Male; Nitrogen Compounds; Occupational Diseases; Occupational Exposure; Pepsinogen A; Prognosis; Retrospective Studies; Siberia

The levels of serum gastrin-17 (G-17) and pepsinogen-1 (P-1) were studied in 54 patients with duodenal ulcerative disease (UD) who worked at chemical plants manufacturing nitrogenous compounds and in 15 healthy individuals (a control group). There are objective data on the time course of changes in the functional characteristics (G-17 and P-1) of the gastric mucosa (GM) in the patients with duodenal UD, which vary with the chemical compositions of hazardous substances and the length of service at a chemical plant. Basic therapy for UD causes positive changes in the functional parameters reflecting the state of GM.

Topics: Adult; Chemical Industry; Duodenal Ulcer; Gastrins; Humans; Male; Middle Aged; Nitro Compounds; Occupational Exposure; Pepsinogen A

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Chronic Disease; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Pyloric Antrum; Retrospective Studies; Stomach Neoplasms; Stomach Ulcer

To study trends in morphological changes of gastric mucosa (GM) and its functional characteristics (serum gastrin-17, pepsinogens I and II) in eradication of Helicobacter pylori (HP) in patients with duodenal ulcer (DU).. HP infection was detected with a rapid urease test, morphological study of gastrobiopsies and polymerase chain reaction in 59 patients with DU. The results of HP eradication were assessed two months after the treatment. Morphological study of gastrobiopsies, assays for gastrin-17, pepsinogens I and II in blood serum were made before the treatment and one year after HP eradication.. By the results of eradication two groups were formed: with effective eradication and uneffective eradication of H. pylori. Examination of GM one year after successful H. pylori eradication in DU patients GM inflammation relieved: reduction in polymorphonuclear (by 42.6%), mononuclear (by 29.3%) infiltration and number of lymphocytic follicules (16.8-fold). GM atrophy decreased by 47.8%. In patients with uneffective eradication the above positive changes were not registered. After H. pylori eradication, serum gastrin-17 lowered by 46. 7%, pepsinogen I--by 30.5%, pepsinogen II--by 36.9%. In uneffective eradication this decrease did not occur.. H. pylori eradication leads to positive changes in morphological and functional indices reflecting GM condition.

Topics: Adult; Anti-Bacterial Agents; Biomarkers; Biopsy; DNA, Bacterial; Duodenal Ulcer; Female; Follow-Up Studies; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Intestinal Mucosa; Male; Pepsinogen A; Pepsinogen C; Polymerase Chain Reaction; Treatment Outcome

In rats, changes in gastric nerve fibers containing gastrin-releasing peptide (GRP) in cysteamine-induced duodenal ulcer were investigated in relation to the dynamics of gastrin-producing cells (G-cells). Marked increases in gastric acid secretion and serum gastrin level were observed from 2 h after the administration of cysteamine. The number of G-cells was significantly decreased from 2 h after the injection of cysteamine. Two and 4 h after the administration of cysteamine, the G-cells showed ultrastructural changes characterized by a markedly decreased number of secretory granules. Circulating GRP levels were significantly elevated from 2 h after the administration of cysteamine. In the control group given vehicle only, nerve fibers showing immunoreaction for GRP formed a fine network in the gastric wall and were densely distributed in the oxyntic mucosa, located close to capillaries and demonstrated varicosities that contained either small clear vesicles or GRP-immunopositive vesicles with large cores. Eight h after the administration of cysteamine, there was depleted GRP immunoreactivity, evidenced by a markedly decreased number of vesicles, with large electron-dense cores, in the oxyntic mucosa. These findings suggest that, in cysteamine-induced duodenal ulcer, alterations in gastric nerve fibers containing GRP may be related to hypergastrinemia.

Topics: Animals; Cell Count; Cysteamine; Duodenal Ulcer; Follow-Up Studies; Gastric Acid; Gastric Mucosa; Gastrin-Releasing Peptide; Gastrins; Immunohistochemistry; Male; Microscopy, Immunoelectron; Nerve Fibers; Peptides; Radiation-Protective Agents; Radioimmunoassay; Rats; Rats, Wistar; Stomach

To understand the short-term and long-term effects of the eradication of Helicobacter pylori on serum pepsinogen I, gastrin, and insulin concentration, we studied 53 patients with endoscopically proven duodenal ulceration and H. pylori infection.. All patients received a 2-wk course of colloidal bismuth subcitrate, amoxycillin, and metronidazole, and endoscopy was performed at 1.5, 3, 6, and 12 months after entry. H. pylori status was assessed by a urease test and histology.. Among 43 patients in whom H. pylori was eradicated throughout the follow-up year, the mean basal pepsinogen I was 108 ng/ml at pretreatment, decreasing significantly to 85, 77, 80, and 75 ng/ml at 1.5, 3, 6, and 12 months, respectively, at posttreatment. The basal gastrin was 100 pg/ml at pretreatment and fell significantly to 72, 64, 65, and 59 pg/ml, respectively, posttreatment. Of the four patients in whom the H. pylori was not eradicated, there was no significant change in the median basal pepsinogen I and gastrin concentration. Among the six patients in whom the H. pylori was again detectable within the follow-up year, the fallen serum concentration of pepsinogen I and gastrin returned to the pretreatment level. There was no significant change of basal insulin concentration after triple therapy in either the successfully eradicated or failed group.. We conclude that H. pylori is the leading and direct cause of higher serum concentration of pepsinogen I and gastrin in duodenal ulcer patients.

Topics: Amoxicillin; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Female; Follow-Up Studies; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Insulin; Male; Metronidazole; Middle Aged; Organometallic Compounds; Pepsinogens; Time Factors

Helicobacter pylori infection increases the serum concentration of gastrin, and this may be one of the mechanisms by which it predisposes to duodenal ulceration. Different forms of circulating gastrin were studied both basally and postprandially in 13 duodenal ulcer patients before and one month after eradication of H pylori. Three antisera that are specific for particular regions of the gastrin molecules were used. Gel chromatography indicated that > 90% of the circulating gastrin consisted of gastrin (G) 17 and G34 both before and after eradicating the infection. The basal median total immunoreactive gastrin concentration fell from 26 pmol/l (range 11-43) to 19 pmol/l (8-39) (p < 0.05), entirely because of a fall in G17 from 6 pmol/l (< 2.4-25) to < 2.4 pmol/l (< 2.4-23) (p < 0.001). The median (range) basal G34 values were similar before (15 pmol (2-36)) and after (10 pmol (2-30)) eradication. The median total immunoreactive gastrin concentration determined 20 minutes postprandially fell from 59 pmol/l (38-114) to 33 pmol/l (19-88) (p < 0.005), and again this was entirely the result of a fall in G17 from 43 pmol/l (9-95) to 17 pmol/l (< 2.4-52) (p < 0.001). The median postprandial G34 values were similar before (13 pmol/l, range 6-42) and after (15 pmol/l, range 6-30) eradication. Eating stimulated a noticeable rise in G17 but little change in G34, both in the presence and absence of H pylori. The finding that H pylori infection selectively increases G17 explains why the infection causes mainly postprandial hypergastrinaemia. G17 is increased selectively because H pylori predominantly affects the antral mucosa which is the main source of G17 whereas G34 is mainly duodenal in origin. This study also indicates that the increased concentration of gastrin in H pylori infection is the result of an increase in one of the main biologically active forms of the hormone.

Topics: Adult; Duodenal Ulcer; Eating; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Protein Precursors

The effect of ulcer healing with eradication of Helicobacter pylori (H pylori) on gastric function was investigated in nine patients with duodenal ulcer disease. One month after eradication there were significant reductions in both basal plasma gastrin concentration, from a median (range) of 19 (1-22) to 6 (2-15) pmol/l (p < 0.05), and of basal acid secretion from 8.3 (2.4-24) to 2.6 (1.4-8.1) mM H+/h, (p < 0.01). The peak acid secretion rate was unchanged from 37 (16-59) to 37 (21-59) mM H+/h. After treatment there was no change in the parietal cell sensitivity to stepped infusions of gastrin heptadecapeptide: the median concentration of gastrin required for 50% of maximal acid secretion (EC50) was 41 (14.8-126) before and 33 (23-125) pmol/l after eradication of H pylori. The metabolic clearance rate of gastrin was also unaffected by the eradication of H pylori. Thus eradication of H pylori infection from patients with active duodenal ulcers is accompanied by falls in both basal gastrin release and basal acid secretion without a change in the parietal cell sensitivity to gastrin. Cyclical changes in H pylori infection may cause the variations in basal acid secretion that are seen in duodenal ulcer disease.

Topics: Acute Disease; Adult; Aged; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Parietal Cells, Gastric; Tetracycline

We calculated gastric HCO3- and H+ secretion, as well as nonparietal and parietal volume secretion, in 15 duodenal ulcer patients who had previously undergone successful proximal gastric vagotomy, 15 unoperated duodenal ulcer patients, and 15 normal control subjects. Basal HCO3- secretion was not significantly altered after vagotomy, while basal H+ secretion, parietal volume and nonparietal volume secretion were reduced significantly. Intravenous gastrin-17 infusion reduced gastric HCO3- secretion by approximately 50% in both unoperated ulcer patients and normal subjects (P less than 0.05). Gastrin-17 infusion did not inhibit gastric HCO3- secretion after vagotomy. In fact, mean gastric HCO3- secretion increased to a nearly significant extent in response to gastrin (P = 0.06). These findings indicate that gastrin inhibits gastric HCO3- secretion in humans and that the gastrin-induced reduction in gastric HCO3- secretion is dependent upon intact vagal innervation to the oxyntic mucosa.

Topics: Bicarbonates; Depression, Chemical; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Secretory Rate; Vagotomy, Proximal Gastric

Serum gastrin concentrations were measured using antisera with specificity for the carboxyl and amino terminus of gastrin-17 in 50 healthy subjects and 18 patients with active duodenal ulcer disease (DU). The amino terminal of gastrin-17 immunoreactivity was significantly higher in DU patients than in healthy subjects. NH2-terminus of gastrin-17 immunopurified material from serum of DU patients was subjected to Sephadex G50 column chromatography and eluates were monitored by an additional antiserum EG10 that recognizes COOH-terminally extended gastrin. Besides the NH2 terminal tridecapeptide of gastrin-17, COOH-terminally extended progastrin was found. This may reflect abnormal processing of gastrin in patients with active duodenal ulcer disease.

Topics: Adolescent; Adult; Aged; Amino Acid Sequence; Duodenal Ulcer; Female; Gastrins; Humans; Immune Sera; Male; Middle Aged; Protein Precursors

Serum gastrin concentrations and gastric acid secretion were measured during intravenous infusion of gastrin heptadecapeptide (G-17) (0, 7, 22.1, 70, 221, and 700 pmol/kg X h) in 15 duodenal ulcer patients and 15 healthy controls. Ulcer patients developed higher serum gastrin concentrations during G-17 infusion due to nearly twofold slower clearance of gastrin (8.8 vs. 15.7 ml/kg X min; P less than 0.01). Despite slower clearance of G-17, ulcer patients had plasma elimination half-times for G-17 similar to controls (6.0 vs. 6.1 min, respectively). Thus, calculated volume of distribution for G-17 was lower in ulcer patients than controls (78.5 vs. 140.7 ml/kg; P less than 0.025). For any serum gastrin during gastrin-17 infusion, acid secretion (millimoles per hour) was higher in ulcer patients than in controls. However, when acid secretion was expressed as a percentage of peak acid output to G-17 (to correct for differences in parietal cell mass), curves relating acid secretion to serum gastrin were identical in ulcer patients and controls.

Topics: Adult; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Half-Life; Humans; Kinetics; Male; Metabolic Clearance Rate; Middle Aged

Gastric acid and pepsin secretion and serum gastrin concentrations were measured in nine patients with uncomplicated duodenal ulcer (DU) and 10 normal controls in the fasting state and in response to graded doses of bombesin, a tetradecapeptide gastrin releaser, and, for reference, synthetic gastrin G-17. Serum gastrin with bombesin stimulation was significantly greater in duodenal ulcer (maximum 467 pg/ml) than in controls (153 pg/ml), while in seven of the DU group tested gastrin levels after a meal were not different from that seen in five of the normal controls. Gastric acid concentrations and outputs were greater in duodenal ulcer with both stimuli. Secretory responses were then related to serum gastrin levels; despite increasing gastrin levels with bombesin stimulation, peak outputs achieved with bombesin were only 50% of G-17 maximum in normals and up to 90% of maximum in duodenal ulcer. Up to the point of peak response to bombesin, acid and pepsin outputs were the same with exogenous and endogenous gastrin, ie, bombesin acted only via G-17. Furthermore, in direct comparison of duodenal ulcer and normals with G-17 infusion, acid and pepsin outputs related to serum gastrin were congruent up to 75% of duodenal ulcer maximum, at which point normals reached their maximum level. These data have shown that duodenal ulcer patients are not more sensitive to either exogenous or endogenous gastrin; we have also shown regulatory defects in duodenal ulcer patients not previously described: an exaggerated release of gastrin with bombesin stimulation, and a defective inhibition of acid and pepsin secretion with higher doses of bombesin.

Topics: Adult; Bombesin; Dose-Response Relationship, Drug; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Hormones; Humans; Male; Pepsin A; Stimulation, Chemical

The sulfation of gastrin in serum, antrum and duodenum was studied in 22 normo- and 20 hypergastrinemic patients. The ratio between gastrin-17 and gastrin-34 was measured in antrum and duodenum. The degree of sulfation was reduced in the antrum of hypergastrinemic patients (35.3 +/- 1.3%, mean +/- SEM) compared with 48.0 +/- 2.1% in normo-gastrinemic patients (p less than 0.001). The degree of sulfation in serum and duodenum was similar to that of the antral gastrins in all patients. The percentage of gastrin-34 in antrum was increased (7.3 +/- 0.7%) in hypergastrinemic compared with 4.9 +/- 0.3% in normogastrinemic patients (p less than 0.01). In the duodenum the percentage of gastrin-34 was similar in normo- and hypergastrinemia. When classified according to clinical diagnosis, sulfation of antral gastrin was normal in duodenal ulcer (47.6 +/- 4.5%) but decreased in gastric ulcer (36.7 +/- 1.6%, p less than 0.01) and pernicious anemia (31.3 +/- 1.9%, p less than 0.001) compared with 48.2 +/- 2.2% in control patients. In pernicious anemia a larger proportion of antral gastrins occurred as gastrin-34 (8.2 +/- 0.9%) compared with 4.8 +/- 0.4% in control patients (p less than 0.01). Our study suggests that both sulfation and proteolytic processing of the gastrin precursor is diminished in hypergastrinemia of antral origin.

Topics: Anemia, Pernicious; Duodenal Ulcer; Gastrins; Gastritis; Gastritis, Atrophic; Humans; Protein Precursors; Pyloric Antrum; Radioimmunoassay; Stomach Ulcer; Sulfuric Acids

The fasting concentrations of total gastrin and gastrin-17 (G-17) were similar in healthy volunteers and in asymptomatic patients with gastric ulcers or duodenal ulcers. However, the fasting serum concentration of gastrin-34 (G-34) was higher in patients with gastric ulcers than in normal subjects, in whom it was higher than in patients with duodenal ulcers. In response to food, the increases in G-17, G-34, and total gastrin were greater in ulcer patients than in healthy subjects. Cimetidine administration was associated with further increases in G-17, G-34, and total gastrin in normal subjects and gastric ulcer patients after meals. The ratio G-17/G-34 was similar in placebo-treated normal subjects and placebo-treated patients with gastric or duodenal ulcers. Cimetidine produced an increase in G-17/G-34 in placebo-treated normal subjects and placebo-treated patients with gastric or duodenal ulcers, but the ratio G-17/G-34 was greater in patients with gastric ulcers than in normal subjects. These results indicate that: differences in serum gastrin concentrations between patient groups, treatment regimens, and time of day are better detected by measuring G-17 and G-34 rather than total gastrin; there are differences in fasting and food-stimulated gastrin concentrations between normal subjects and patients with gastric or duodenal ulcers; the fasting concentration of G-34 is higher than G-17 in normal subjects and patients with gastric ulcers but not in patients with duodenal ulcers; food increases G-17 in all subjects but G-34 only in subjects with gastric ulcers; cimetidine increases the fasting concentration of total gastrin in normal subjects and patients with gastric ulcers and increases G-17 and G-34 in normal subjects; cimetidine increases the ratio G-17/G-34 in normal subjects and patients with gastric ulcers, but decreases G-17/G-34 in patients with duodenal ulcers. It is proposed: that measurements of total gastrin concentration should be replaced by measurements of G-17 and G-34 and that such measurements of G-17 and G-34 indicate differences in serum gastrin concentrations between normal subjects and those with peptic ulcers and between those with gastric versus duodenal ulcers. The role of altered gastrin metabolism in the pathogenesis of ulcers needs to be established.

Topics: Cimetidine; Duodenal Ulcer; Eating; Gastrins; Humans; Protein Precursors; Stomach Ulcer; Time Factors

Topics: Duodenal Ulcer; Gastrins; Humans; Radioimmunoassay

The concentrations of gastrins containing the active C-terminal tetrapeptide amide (mainly gastrin-34 and gastrin-17) and the N-terminal tridecapeptide fragment of gastrin-17 were measured in antral and duodenal biopsy specimens. The antral concentration of the N-terminal gastrin fragment was much higher in patients with active duodenal ulcer (33.4 +/- 6.8 nmol g-1, mean +/- SEM, n = 15) than in controls (5.6 +/- 2.9 nmol g-1, n = 10), patients with gastric ulcer (5.6 +/- 1.8 nmol g-1, n = 10) or patients with pernicious anaemia (7.7 +/- 2.5 nmol g-1, n = 6). No differences were found between the groups regarding gastrin-34 and gastrin-17 concentrations. In duodenal extracts, the N- and C-terminal gastrin concentrations were similar in all groups of patients. These data suggest that the posttranslational processing of antral gastrin is abnormal in patients with active duodenal ulcer disease.

Topics: Adult; Aged; Anemia, Pernicious; Chromatography, Gel; Duodenal Ulcer; Female; Gastrins; Hormones; Humans; Male; Middle Aged; Protein Precursors; Pyloric Antrum; Radioimmunoassay; Stomach Ulcer

A dose response study of the effect on gastric acid secretion of synthetic human gastrin-17 in doses of 50,200, and 500 ng/kg/h was performed in eight healthy volunteers and in eight patients with duodenal ulcer. The study was repeated on a separate day during intravenous infusion of calcium gluconate (0.1 mmol Ca2+/kg/h). In healthy subjects the acid response to the combined infusion of synthetic human gastrin and calcium did not significantly exceed the response to synthetic human gastrin alone, in contrast with patients with duodenal ulcer in whom the combined infusion did significantly improve acid output compared with infusion of synthetic human gastrin alone. The dose of synthetic human gastrin required for half maximal acid response (D50) was reduced in both groups but significantly more in patients with duodenal ulcer. No difference in serum gastrin concentrations or in serum calcium concentrations were found. It is hypothesised that extracellular calcium plays a role in gastrin stimulated acid secretion in man and that patients with duodenal ulcer are more sensitive to this calcium dependent mechanism than non-duodenal ulcer subjects.

Topics: Adult; Calcium Gluconate; Dose-Response Relationship, Drug; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Gluconates; Hormones; Humans; Male; Middle Aged

A comparison was made between use of isotonic 0.15 M sodium chloride and 5.8 g/100 ml glucose solutions for measurement of gastric acid secretion by intragastric titration in normal and ulcer subjects. Glucose distention did not cause significantly different acid secretion than saline distention in either group. The total amounts of glucose entering the duodenum over the 3.5-hr study period were 99 g in normal subjects and 122 g in ulcer subjects. In normal subjects, circulating gastrin-related acid secretion curves were not significantly different during endogenous peptone and exogenous G-17 stimulation using either the glucose or the saline meals. This finding provides evidence that glucose meals of this size do not alter sensitivity to gastrin. With glucose meals, inhibition of gastric emptying caused retention of a sufficient volume in the stomach to permit accurate continuous intragastric titration. Saline meals caused pronounced diarrhea which was not seen after glucose meals. Glucose distention intragastric titration allows reliable comparisons of endogenously and exogenously stimulated gastric acid secretion without serious side effects and is especially suitable for studying acid secretion in duodenal ulcer subjects.

Topics: Adult; Aged; Duodenal Ulcer; Evaluation Studies as Topic; Food; Gastric Acid; Gastric Acidity Determination; Gastric Emptying; Gastrins; Glucose; Humans; Infusions, Parenteral; Male; Middle Aged; Peptones; Sodium Chloride; Time Factors

A newly synthesized human big gastrin (G34) that was prepared according to the revised structure and that contained less than 3% oxidized methionine residues was compared with synthetic human little gastrin (G17) for acid-stimulating activity and clearance in human subjects. Prolonged infusions of each type of gastrin revealed that the time required to approach stable plasma concentrations was much longer for G34 than for G17. The time course of plasma gastrin concentration could be described by one-compartment models with half-lives of 44 min for G34 and 8 min for G17. After rapid intravenous infusion, G34 produced a much larger total acid response than did an equimolar dose of G17, and the responses were directly proportional to the integrated plasma gastrin increments. During the third hour of prolonged intravenous infusions of G34 and G17, the exogenous dosage of G34 required to produce the same blood concentration of gastrin was only one-fourth that of G17. Equivalent blood concentrations of G34 and G17 were associated with similar rates of acid secretion. These results suggest that G34 is more potent than has been thought, that it has an activity similar to that of G17 and that it must not be ignored in estimating total acid-stimulating activity of circulating gastrins. The measurement of total carboxyl-terminal immunoreactive gastrin can produce a good estimate of total acid-stimulating activity.

Topics: Adult; Aged; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Injections, Intravenous; Male; Middle Aged; Protein Precursors; Radioimmunoassay

After a meal the serum concentrations of the N-terminal tridecapeptide-like fragment of gastrin-17, (1-13)G-17, increased markedly in patients with active duodenal ulcer, but less so in healthy subjects. Consequently the synthetic (1-13)G-17 was infused intravenously in doses that resulted in concentrations similar to those measured in duodenal ulcer patients in order to examine whether the N-terminal fragment influences gastric acid secretion. Doses of 125 and 400 pmol (1-13)G-17/kg per h inhibited the meal-stimulated acid secretion by 36% (P less than 0.05) and 66% (P less than 0.05) respectively. The release of endogenous C-terminal gastrin immunoreactivity was not influenced. The infusion of (1-13)G-17 also inhibited the acid response to exogenous gastrin-34, gastrin-17 and Peptavlon, but not to gastrin-4. The results suggest that the N-terminal gastrin-17 fragment--although devoid of the hitherto considered only active site of gastrin--plays a significant role in the regulation of the gastric acid secretion in patients with active duodenal ulcer.

Topics: Adult; Binding Sites; Depression, Chemical; Duodenal Ulcer; Fasting; Female; Food; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Peptide Fragments

The metabolism of the NH2-terminal tridecapeptide fragment of gastrin-17 (1-13)G-17) was examined in normal subjects and duodenal ulcer patients. A dose of 65 pmol synthetic human (1-13)G-17/kg/h was infused intravenously for 90 min. After cessation of infusion the disappearance curve was similar in the two groups. The mean half-life, volume of distribution, and clearance rate were, for normal and duodenal ulcer subjects, 6.3 and 6.3 min, 100 and 93 ml/kg, and 11.0 and 10.2 ml/kg/h, respectively. The gastric acidity decreased during the infusion in duodenal ulcer patients (54 +/- 11 to 40 +/- 10 meq/l (p less than 0.02] but not in normal subjects. The results suggest that the increased serum concentrations of the NH2-terminal fragment of gastrin-17 in duodenal ulcer patients are not caused by a decreased metabolism of (1-13)G-17. Moreover, the data show that (1-13)G-17 reduces gastric acid secretion.

Topics: Adult; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Injections, Intravenous; Male; Middle Aged; Peptide Fragments

The concentration of the NH2-terminal fragment of gastrin-17 in serum was determined by radioimmunochemistry. Two antisera were used, one specific for the COOH-terminus and the other for the NH2-terminus of gastrin-17. The NH2-terminal gastrin-17 immunoreactivity in unfractionated serum correlated well with the amount of fragment found after gel filtration of the same sera (p less than 0.001). In healthy subjects (no. = 100), the NH2- and COOH-terminal gastrin immunoreactivity was 8 +/- 1 and 20 +/- 1 pmol/l (mean +/- SEM), respectively. In patients with acute duodenal ulcer (no. = 30) and acute gastritis (no. = 10) the NH2-terminal immunoreactivity was fourfold increased compared with in healthy subjects (p less than 0.001), whereas the COOH-terminal was identical, the NH2- and COOH-terminal concentrations being 33 +/- 7 and 22 +/- 2 pmol/l in duodenal ulcer and 35 +/- 6 and 21 +/- 1 pmol/l in acute gastritis. Other groups of patients had NH2- and COOH-terminal gastrin concentrations in serum similar to those measured in healthy subjects. The results suggest that gastrin cells process gastrin-17 abnormally during the acute phase of duodenal ulcer and gastritis.

Topics: Acute Disease; Adolescent; Adult; Aged; Amino Acid Sequence; Chromatography, Gel; Duodenal Ulcer; Female; Gastrins; Gastritis; Humans; Male; Middle Aged; Peptide Fragments; Radioimmunoassay

Topics: Chromatography, Affinity; Chromatography, Gel; Duodenal Ulcer; Duodenum; Gastrectomy; Gastrins; Humans; Protein Precursors; Pyloric Antrum; Radioimmunoassay