Radioimmunoassay of gastrin

RELEASING factors1 and other brain peptides2 have been the subject of extensive studies and the high sensitivity of modern measurement techniques has led to the discovery, in various tissues3,4 and in the nervous system5–9, of new, unpredicted locations for otherwise well known peptides. Evidence for the presence in the vertebrate nervous system of a hitherto undescribed brain gastrin immunoassayable peptide (BGP) is presented here.

New peptide in the vertebrate CNS reacting with antigastrin antibodies.

It is proposed that two types of atrophic gastritis, Type A and B, can be distinguished in man on the basis of the distribution of the disease in the stomach and results of autoimmune serologic tests. In Type A gastritis the test for parietal cell antibody (PCA) is positive and serum gastrin levels are high, reflecting an intact antral mucosa demonstrable also by biopsy. Corpus changes are diffuse and gastric secretion of acid severely impaired. In Type B gastritis the test for PCA is negative and serum gastrin levels are low, reflecting antral damage. Corpus changes tend to be focal and gastric secretion of acid is moderately to severely impaired. Chronic gastritis occurs frequently (prevalence, 28%) in Caucasian adult populations, Type B being four times more frequent than Type A. Several endocrine diseases and other organ-specific autoimmune reactions are strongly linked to Type A gastritis; pernicious anemia evolves almost exclusively from this type. Gastrointestinal symptoms, gastric hemorrhage and gastric ulcer are prominent sequelae of Type B gastritis. Iron deficiency and gastric carcinoma can develop from both forms of gastritis, but Type B is the more important precursor of carcinoma. Autoimmunity is believed to be of primary importance in Type A gastritis and is probably genetically determined. Environmental factors, including several mucosal “irritants” may determine the occurrence of Type B gastritis.

A reappraisal of the nature and significance of chronic atrophic gastritis.

In order to produce antibodies for use in radioimmunochemical determination of gastrin in serum, 41 guinea pigs and 72 rabbits were immunized; 15 different immunization schemes were employed; 23 animals (1 guinea-pig and 22 rabbits) produced detectable antibodies to gastrin. The antisera could bind 50% of 3 fmol (˜ 7 pg) 125I-gastrin in dilutions varying from 1:125 to 1:128,000. The binding energy expressed by the average association constant, K0, ranged from the order of 107l/mol to 1012l/mol. Only three antisera had antibodies with sufficient binding energy for radioimmunochemical determination of low physiologic concentrations of serum-gastrin (K0≥1011l/mol). One of these antisera reacted with cholecystokinin to an extent that made it unsuited for gastrin determinations in biologic fluids. The remaining two antisera were both in respect to dilution, binding energy, and specificity well suited to radioimmunoanalysis of gastrin in serum. On the basis of binding studies it appeared that 11 of the 23 gastr...

Production and evaluation of antibodies for the radioimmunoassay of gastrin.

Chylous ascites: a collective review.

A radioiodine-immunoassay technic was used to measure fasting serum gastrin levels in four patients with the Zollinger-Ellison syndrome and 24 patients without gastrointestinal diseases. Serum gastrin levels in all the patients with the Zollinger-Ellison syndrome exceeded by approximately tenfold or greater the mean serum gastrin level of 425 μμg per milliliter in the control population. Gastrin was identified immunochemically in an extract derived from a pancreatic islet-cell tumor from one of the patients with the Zollinger-Ellison syndrome.

Immunochemical measurement of elevated levels of gastrin in the serum of patients with pancreatic tumors of the Zollinger-Ellison variety.

Fasting and postprandial (two hour) venous gastrin concentrations were measured in serums from a population of 29 patients with pernicious anemia and compared with a control population of patients. Mean fasting and postprandial gastrin concentrations for the patients with pernicious anemia were 997 (± 182 S.E.) and 1007 (± 303 S.E.) pg per milliliter respectively, whereas fasting and postprandial serum gastrin levels for the control patients were 165 (± 28 S.E.) and 209 (± 55 S.E.) pg per milliliter. The differences are significant (p less than 0.025). Among the patients with pernicious anemia nine of 29 (31 per cent) had serum gastrin levels sufficiently elevated to be considered in the hypergastrinemic range characteristic of the Zollinger — Ellison syndrome.

Serum Gastrin Concentrations in Pernicious Anemia

Serum gastrin levels were repeatedly measured in a patient with a total gastrectomy and hypergastrinemia associated with the Zollinger—Ellison syndrome. Fasting serum concentrations determined on consecutive days, and also at four-hour intervals during a 24-hour period, revealed persistent hypergastrinemia that varied within a relatively narrow range. Serum gastrin levels were found to relate directly to plasma calcium concentrations, falling by a factor of 20 with the development of hypocalcemia after parathyroidectomy for hypercalcemic hyperparathyroidism. Marked increases in serum gastrin concentration were induced by calcium infusion (12 and 20 mg per kilogram of body weight) but not by infusion of parathormone. The previously demonstrated effects of calcium in the control and stimulation of gastric acid secretion may be mediated by the polypeptide hormone gastrin.

Effects of Calcium on Serum Gastrin Levels in the Zollinger–Ellison Syndrome

Studies with antibodies to gastrin. Radioimmunoassay in human serum and physiological studies.

Fasting venous serum gastrin concentrations and both unstimulated and maximum-stimulated gastric hydrochloric acid secretory rates were determined in 168 subjects. The patients included 55 with duodenal peptic-ulcer disease, nine with gastric ulcers and 69 with assorted gastrointestinal abnormalities, and 35 control subjects without recognized gastrointestinal diseases. Fasting serum gastrin concentrations were measured by radioimmunoassay and compared for groups of patients with differing rates of basal and stimulated gastric acid secretion. There was, in general, an inverse relation between fasting serum gastrin concentrations and rates of gastric hydrochloric acid secretion. Fasting serum gastrin concentrations in patients with duodenal-ulcer disease were not found to be significantly greater than those of the control subjects. However, mean serum gastrin concentrations in the patients with gastric-ulcer disease were found to be significantly greater than those of both the control subjects and...

Walter L. Trudeau

Papers

Immunochemical measurement of elevated levels of gastrin in the serum of patients with pancreatic tumors of the Zollinger-Ellison variety.

Serum Gastrin Concentrations in Pernicious Anemia

Effects of Calcium on Serum Gastrin Levels in the Zollinger–Ellison Syndrome

Studies with antibodies to gastrin. Radioimmunoassay in human serum and physiological studies.

Relations between Serum Gastrin Levels and Rates of Gastric Hydrochloric Acid Secretion