Total Gastrin Research Articles

Analytical and Clinical Performance of a Liquid Chromatography-Tandem Mass Spectrometry Method for Measuring Gastrin Subtypes G34 and G17 in Serum.

Two major forms of gastrin, gastrin-17 (G17) and gastrin-34 (G34), exist in blood. However, conventional immunoassay methods can only quantify total gastrin or G17 alone. Here, we aimed to establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify G17 and G34 simultaneously. Serum samples were prepared by anion-exchange solid-phase extraction. The analytical performance of the LC-MS/MS method was validated and the method was compared to chemiluminescence immunoassay (CLIA) and radioimmunoassay (RIA). The G17 and G34 concentrations in 245 serum samples from healthy controls, individuals with gastrinoma, and individuals with other diseases were analyzed. The total runtime of the LC-MS/MS method was 6 min. No substantial matrix effect was observed with internal standard correction. The intraassay coefficients of variation (CVs) for G17 and G34 were 4.0%-14.2% and 4.4%-10.4%, respectively, and total CVs were 5.2%-14.1% and 4.6%-12.4%, respectively. The correlation coefficient between LC-MS/MS and CLIA was 0.87, and between LC-MS/MS and RIA was 0.84. The G17+G34 concentrations for 87.5% of individuals with gastrinoma were higher than the 95th percentile of healthy controls (18.1 pg/mL), whereas the concentrations for individuals with other diseases and gastrinoma overlapped. Based on the Youden indices calculated for G17+G34, G34, and G17, the most specific biomarker was G17 (96.9% clinical specificity at 209.8 pg/mL) for gastrinoma. This method should aid in the diagnosis of diseases associated with increased gastrin concentrations.

Analytical aspects of gastrin measurement in neuroendocrine tumors

Rationale:Biochemical diagnostics of neuroendocrine tumors (NETs) is based on the analysis of universal and specific markers, according to the tumor type and clinical manifestations of the disease. Measurement of gastrin levels in the serum of NETs patients is important in the diagnosis of the functioning pancreatic, gastric and duodenal NETs.Aim:To perform a comparative analysis of the results of gastrin measurement as a biochemical marker of NETs using different test-systems.Materials and methods: Serum gastrin was measured in the serum of 30 NET patients and 18 normal controls by immunochemiluminescent (Immulite 2000 Gastrin, “Siemens”) and ELISA (Gastrin-17 ELISA, “Biohit”) assays.Results:The analysis of the results of gastrin measurement by immunochemiluminescent and ELISA methods showed significant variability of its levels, reaching 2016 and 1988 pmol/l, respectively. Comparable analytical sensitivity of the two test systems was confirmed by similar increases (over 30- to 40-fold) of the median levels of the hormone in the serum of patients with gastric NETs, compared to healthy controls. The analysis of diagnostic efficacy accounting for their respective cut-offs demonstrated higher sensitivity (95.4%) of the Immulite 2000 Gastrin test-system, which measures total gastrin, than that of the ELISA method (80.0%), specific to gastrin-17.Conclusion:The analysis shows high efficacy of immonochemiluminescent method of measurement of total gastrin as a biochemical marker of NETs.

Circulating gastrin concentrations in patients at increased risk of developing colorectal carcinoma

An increase in circulating concentrations of gastrin or gastrin precursors such as progastrin and glycine-extended gastrin has been proposed to promote the development of colorectal carcinomas (CRC). The aim of this study was to investigate whether or not circulating gastrin concentrations were increased in patients with an increased risk of developing CRC. Patients were divided according to their risk into the five following groups: familial adenomatous polyposis (n = 20), hereditary non-polyposis colorectal cancer (n = 53), cluster of common colorectal cancers (n = 13), personal history and/or family history of adenomatous polyps or CRC (n = 150) and controls (n = 42). Radioimmunoassay with four region-specific gastrin antisera was used to measure progastrin, glycine-extended gastrin (gastrin-gly), amidated gastrin (gastrin-amide), and total gastrin in peripheral blood taken at the time of colonoscopy. Compared with the control group, familial adenomatous polyposis patients had significantly higher median values of total gastrin (29.8 pM vs 16.9 pM, P = 0.003) and gastrin-amide (17.1 pM vs 12.0 pM, P = 0.015). Patients with a personal or family history of adenomatous polyps or CRC also had higher circulating concentrations of total gastrin (21.8 pM) compared with controls (P < 0.05), while patients from all groups who presented with an adenomatous polyp on the day of colonoscopy had higher concentrations of total gastrin, progastrin, and gastrin-amide than patients without polyps. Concentrations of gastrin precursors are increased in particular groups with an increased risk of developing CRC.

GastroPanel: Different patterns in H. pylori infected and coeliac disease children

Aim. GastroPanel combines the evaluation of pepsinogens A and C PGA, PGC), anti-H. pylori antibodies (Ab) and gastrin-17 (G17) to identify astric mucosal inflammation and atrophy. We analysed GastroPanel in H. ylori infected (Hp+) and coeliac disease (CD) children. Methods. Five hundred and forty-five children subjected to EGDS. In asting sera: PGA, PGC, G17, Ab (ELISAs) and total gastrin (tG) (RIA). In astric juice: pH. Histology for inflammation, Hp and CD diagnosis. Results. Eighty-nine Hp+, 45 CD and 411 Hp and CD negative (conrol children). PGC and Ab were higher in Hp+ than in controls (F= 12.2, < 0.001; F= 35.6, p< 0.001). PGA/PGC was reduced in Hp+ (6.8± 0.44, ean±S.E.M.) and in CD (6.7± 0.67) with respect to controls (10.1± 0.52) F= 6.25, p< 0.005). tG and G17 were higher in Hp+ (67.6± 3.2 ng/l and .0± 1.7 pmol/l) and CD (103.4± 23.6 and 8.6± 2.3) than in controls 61.2± 2.4 and 3.2± 0.4) (F= 9.23, p< 0.001; F= 9.48, p< 0.001). PGC, b and G17 correlated withHp density grade (F= 6.44, p< 0.005;F= 20.79, < 0.001; F= 7.43, p< 0.005). PGC correlated also with the degree of antral nflammation (F= 6.18, p< 0.005) and activity (F= 9.89, p< 0.001). In Hp+ direct correlation between PGA and tG was found (r= 0.396, p< 0.001); in D this association was opposite (r=−0.388, p< 0.05). In Hp+ intragastric H correlated directly with tG (r= 0.264, p< 0.05); in CD intragastric pH nversely correlated with PGA (r=−0.336, p= 0.06) and directly with tG r= 0.787, p< 0.001) and with G17 (r= 0.609, p< 0.01). In CD histology ailed to demonstrate frank gastric mucosal atrophy. Summary.Hp associated gastritis enhanced serum PGC, Ab and G17. In D the reduced levels of PGA/PGC suggest that atrophy might involve gasric body mucosa, probably with a patchy pattern escaping routine histology; he consequent reduced gastric acid secretion enhanced gastrin release. Conclusion. Hp associated gastritis enhances serum PGC and G17. In D, gastric mucosal atrophy, suggested by the combined PGA/PGC reduced nd G17 increased levels might be extended outside the duodenum affecting he stomach.

Rat progastrin processing yields peptides with altered potency at the CCK-B receptor

Details of prohormone processing patterns are revealed by purification and characterization of molecular forms stored in the tissues where the hormones are expressed. Molecular forms of rat gastrin were purified from antral extracts by gel permeation, anion exchange, and reverse-phase HPLC. Amidated and glycine-extended gastrins were detected with specific antisera and their structures determined by mass spectrometry. In rats, the only form shorter than gastrin-17 observed contained 16 amino acids. These data suggest that two enzymes process the amino terminus of gastrin-17. Pyrrolidone carboxylic acid peptidase removes the amino terminal pyrrolidone carboxylic acid (pyroGlu), forming gastrin-16. In mammals other than rat, gastrin-16 is then cleaved by dipeptidyl peptidase IV to form gastrin-14. In rat, this reaction does not take place because of proline residues Pro 2-Pro 3- in gastrin-16. Gastrin-16 is found in sulfated and nonsulfated forms and comprises 28% of the total gastrin immunoreactivity. Glycine-extended forms of gastrin-16 and gastrin-17 comprises 45% of the total gastrin immunoreactivity. The sulfated forms of gastrin-16 and gastrin-17 bind to the CCK-B receptor transfected into CHO cells with 10-fold higher affinity than the nonsulfated forms of these peptides. Therefore, processing of rat progastrin may modulate the expression of gastrin biological activity.

Plasma levels of progastrin but not amidated gastrin or glycine extended gastrin are elevated in patients with colorectal carcinoma

BACKGROUNDThe relationship between plasma gastrin levels and colorectal cancer is controversial. When confounding factors which increase plasma gastrin levels are taken into account, it has been shown that gastrin levels...

Expression of progastrin-derived peptides and somatostatin in fundus and antrum of nonulcer dyspepsia subjects with and without Helicobacter pylori infection.

The hypergastrinemia and hyperacidity associated with Helicobacter pylori infection has been explained by either a primary excess of gastrin or a lack of inhibitory influence by somatostatin (SOM). The objective of the present study was to compare the concentrations of fundic and antral SOM- and antral progastrin-derived peptides in nonulcer dyspepsia (NUD) subjects with and without H. pylori infection. Antral and fundic mucosal biopsies were extracted and assayed for SOM and gastrin amide, glycine-extended gastrin (gastrin gly), progastrin, and total gastrin. There was a significant sixfold reduction in antral SOM but no change in fundic SOM content in H. pylori-infected subjects compared to uninfected subjects. Antral gastrin amide concentrations were significantly higher in infected subjects. However, the concentrations of the nonamidated gastrin forms (progastrin and glycine-extended gastrin) were significantly lower in the infected subjects, indicating an increased conversion of the precursor forms of gastrin to amidated gastrin, the type known to stimulate gastric acidity. The present study demonstrates that the elevated gastrin concentrations associated with H. pylori infection may be due to a reduction in the paracrine inhibitory effect of SOM on antral gastrin release. In addition, the posttranslational processing of gastrin to the amidated forms is increased in infected subjects, explaining why the elevation in antral gastrin is confined to the amidated form.

Autoantibodies to gastrin in patients with pernicious anaemia--a novel antibody

Autoantibodies arise when there is a breakdown in immunological tolerance. Autoantibodies to parietal cells and intrinsic factor are found in autoimmune atrophic gastritis (AAG) and are associated with elevated plasma gastrin. Endogenous gastrin autoantibodies have not been described to date. The aim of this study was to investigate the occurrence of autoantibodies to gastrin. Plasma from 50,000 patients, including more than 2000 with AAG, was tested. Gastrin was measured by radioimmunoassay (RIA) in whole plasma and the presence of autoantibody determined by using a control which omitted assay antibody. The quantity and affinity of gastrin autoantibodies was assessed. Three patients had autoantibodies to gastrin. All three had AAG and pernicious anaemia (PA). The antibodies were of low titre and relatively high affinity. Free circulating plasma gastrin levels were within the normal range, but total gastrin levels were elevated. This is the first description of autoantibodies to endogenous gastrin. The incidence of antibodies to gastrin is low, they are found in association with PA, and they may lead to falsely low measurements of plasma gastrin.

Effects of enprostil on gastric endocrine secretion during chronic administration of lansoprazole.

We investigated changes in the secretory kinetics of gastric endocrine cells related to the administration of lansoprazole, and the effects of enprostil on these altered kinetics. Male Wistar-derived 8-week-old rats were allotted to a control group, a lansoprazole administration group, an enprostil administration group, and a lansoprazole + enprostil administration group. Lansoprazole (30 mg/kg once a day for 4 weeks) and enprostil (10 micrograms/kg twice a day for 4 weeks) were administered into the gastric lumen with a gastric tube. At this time, blood was collected and immunohistological staining of gastric endocrine cells was conducted to investigate the secretory kinetics. Lansoprazole administration induced hypergastrinemia, increase of gastrin cells, and increase of enterochromaffin-like cells. Enprostil administration induced increase of somatostatin cells. The group administered lansoprazole + enprostil exhibited significant decreases in serum gastrin level, total gastrin cell count, and total enterochromaffin-like cell count, compared with the group administered lansoprazole alone. These findings suggest that enprostil may ameliorate the alteration in gastric endocrine secretion produced by the chronic administration of lansoprazole.

P.6.075 Risperidone in the treatment of neurological disorders

The effects of the microtubule stabilizing agent, deuterium oxide, on in vitro rat antral gastrin release were examined under basal conditions and during stimulation with isobutyl methylxanthine and bombesin plus isobutyl methylxanthine. Basal gastrin release from antral mucosal fragments was unaffected by increasing media concentration of deuterium oxide (12.5 to 75% v/v) during 1 h incubations. Gastrin release stimulated by isobutyl methylxanthine (0.1 mM), a potent inhibitor of phosphodiesterase activity, was inhibited completely by 12.5% deuterium oxide. Bombesin (1 × 10−8 M) in the presence of IBMX (0.1 mM) stimulated gastrin release (29.7 ± 1.9% of total gastrin). This was significantly greater than gastrin released under control conditions and with IBMX alone: 12.0 ± 1.1 (P < 0.001) and 20.2 ± 2.6% of total gastrin (P < 0.02), respectively. Partial inhibition of bombesin-IBMX stimulated gastrin release was achieved with 12.5% and 25% deuterium oxide and stimulation of gastrin release was inhibited completely by 50% deuterium oxide. In contrast to these results, gastrin release stimulated by the calcium ionophore A23187 was not inhibited by 50% deuterium oxide. Additional studies were performed to assess reversibility of the effects of deuterium oxide on stimulated gastrin release. Antral tissue exposed to initial culture medium containing deuterium oxide (50%) and bombesin-IBMX for 60 min was exchanged for medium without deuterium oxide. Restimulation of antral tissue during the second hour of culture resulted in gastrin release that was comparable to that observed in cultures not exposed to deuterium oxide during the first hour of culture. Reversibility of the effects of deuterium oxide suggest that a functional alteration in microtubular function is restored by removal of heavy water from the culture medium. Results of these experiments indicate that deuterium oxide is capable of inhibiting gastrin release stimulated by the peptide hormone bombesin and by the phosphodiesterase inhibitor isobutyl methylxanthine. Furthermore, these results suggest that increased levels of intracellular calcium achieved by the action of ionophore A23187 prevent microtubular stabilization by deuterium oxide.

Gastrin processing and secretion in patients with end-stage renal failure.

Gastrin circulates at higher than normal concentrations in patients with end-stage renal failure (ESRF). However, it remains unclear which forms of gastrin are elevated and whether there is also an alteration in the secretory profile after stimulation. In the present study all processed and partially processed forms of circulating gastrin were measured in plasma before and after meal stimulation in ESRF patients and control subjects. Since Helicobacter pylori (HP) infection affects gastrin secretion, HP status was determined. Fasting gastrin-amide (36 +/- 8 pmol/L), gastrin-Gly (55 +/- 16 pmol/L), and total gastrin (218 +/- 32 pmol/L) measured in ESRF/HP-patients were all significantly greater than those in the control group (10 +/- 1, 15 +/- 3, and 17 +/- 2 pmol/L, respectively; P < 0.01). Plasma gastrin-amide (126 +/- 67 pmol/L) and total gastrin (397 +/- 164 pmol/L) were highest in the ESRF/HP+ patients. The proportion of nonamidated gastrin products was 4-fold higher in ESRF patients than in control subjects, suggesting structure-specific changes in gastrin secretion and metabolism, and this was confirmed by chromatography. The meal-stimulated increments in control/HP- and ESRF/HP-groups were similar. However, the ESRF/HP+ group had a markedly potentiated gastrin response. Fasting plasma somatostatin, an inhibitor of gastrin secretion, was also measured and was significantly lower in the ESRF patients than that in the control group. These studies show that the hypergastrinemia associated with renal failure has been underestimated. This is because only amidated products were measured. The potentiated gastrin meal response in ESRF attributed previously to changes in gastrin metabolism are in part explained by the effect of HP infection. The observed diminished somatostatin response suggests that the increase in circulating gastrin in ESRF is the result of loss of inhibition of secretion as well as decreased metabolism. As both amidated and nonamidated gastrin are now considered to have trophic and secretory effects, these findings may explain the gastrointestinal tract hypertrophy often associated with ESRF.

Expression, processing, and secretion of gastrin in patients with colorectal carcinoma

Background & Aims : The relationship between gastrin and the development of colorectal carcinoma (CRC) remains controversial. Problems with previous studies include failure to measure all forms of gastrin, lack of comparison between stored and secreted gastrin, and not controlling for Helicobacter pylori infection (a known cause of hypergastrinemia). The aim of this study was to quantify progastrin and progastrin-derived peptides in the resected tumor and plasma of patients with CRC and in the antrum and plasma of normal subjects. Methods : Four region-specific gastrin antisera were used to measure progastrin, glycine-extended gastrin, amidated gastrin, and total gastrin. Results : Progastrin, amidated gastrin, total gastrin, and glycine-extended gastrin were detected in 100%, 69%, 56%, and 44% of tumors, respectively (n = 32). When allowing for H. pylori infection, circulating amidated gastrin levels were not significantly elevated in patients with CRC. However, compared with control H. pylori-positive and H. pylori-negative subjects, fasting plasma total gastrin levels were increased in H. pylori-positive (5.2-fold) and H. pylori-negative (2.3-fold) patients with CRC. Conclusions : Gastrin or its processing intermediates are present in a high proportion of CRCs. Nonamidated gastrin levels are elevated in the circulation of patients with CRC regardless of H. pylori status. We conclude that gastrin should continue to be assessed as a circulating or autocrine growth factor in the development of CRC.

Plasma molecular forms of gastrin, neurotensin and somatostatin in pregnancy and gestational diabetes after an oral glucose load or a mixed meal

At present the physiological role of gastrin, neurotensin and somatostatin in pregnancy and gestational diabetes is scarcely known. We have measured their different molecular forms in plasma of six female controls, six normal pregnant (NP) women and six gestational diabetic (GD) women under basal conditions and 30 min after an oral glucose load (100 g) and a liquid mixed meal in order to study if their alteration could contribute to the impaired glucose tolerance in GD. Total basal concentrations of neurotensin and somatostatin were higher in GD than in controls and NP, and no change was found after the glucose load or mixed meal in GD. Neurotensin-1–13 was the main molecular form of all neurotensins at basal time in the three groups studied, being higher in GD in comparison with controls and NP. Somatostatin-1–14 was the predominant molecular form in controls and GD under basal conditions and did not show any change after stimuli. In NP, somatostatin-1–14 showed a significant increase following both kinds of stimuli. Total gastrin concentrations in NP and GD showed a significant increase after the glucose load, which was not observed in controls. Gastrin-17 was the main molecular form at basal time and 30 min post-stimuli in GD but not in NP and controls. We suggest that the basal elevation of neurotensin and somatostatin levels could contribute to the impaired glucose tolerance observed in gestational diabetes, as well as to the lack of post-stimuli responses for neurotensin and somatostatin in GD. The different patterns of circulating small and large molecular forms of neurotensin, gastrin and somatostatin may be due to variations in the rate of their release or degradation in pregnancy and gestational diabetes.

Gastrin and gastrin-related responses to infection with Ostertagia ostertagi in the half

The effects of a single challenge with 60,000 infective Ostertagia ostertagi larvae on blood and gastrointestinal mucosal gastrin concentrations, gastrin-producing G-cell numbers in the pyloric mucosa and growth of different parts of the gut were investigated in 16, two-and-a-half-month-old calves. Infected calves exhibited a rise in abomasal pH which was accompanied by a 145 per cent increase in wet weight of the fundic mucosa (P<0·05) and a significant rise in blood total gastrin concentrations (P<0·01). Circulating little gastrin (G-17) was unaffected. Pyloric mucosal total gastrin concentrations remained unaltered in the infected calves until day 28 when levels fell to 36·9 per cent of control group values (P<0·01). Pyloric mucosal G-cell numbers declined during the experiment in the infected group. It is suggested that release of previously stored tissue gastrin and not a change in Gcell numbers contributes to the hypergastrinaemia associated with ostertagia infection in the calf.

Effects of weaning on plasma levels of prolactin, oxytocin, insulin, glucagon, glucose, gastrin and somatostatin in sows

The effect of total weaning (all piglets were weaned at 35 days of lactation) and fractionated weaning (the heavier half of the litter was weaned on day 33 of lactation and the remainder 2 days later) on plasma levels of prolactin, oxytocin, insulin, glucagon, glucose, gastrin and somatostatin in primiparous sows was studied. Twelve crossbred sows were grouped into six pairs according to farrowing data and litter size. The litter of one sow in each pair was weaned in two stages (treatment), and the other was conventionally weaned (control). Blood samples were collected via a permanent jugular vein catheter every 3 hours from 9 a.m. to 9 p.m. from day 31 of lactation until the third day of final weaning. In response to total weaning (studied in the six control sows), plasma prolactin, glucagon and gastrin decreased significantly, whereas plasma insulin and somatostatin significantly increased. Basal concentrations of plasma oxytocin and glucose remained unchanged after weaning. Fractionated weaning did not result in any significant differences in the hormonal and glucose levels as compared with the total weaning. The possible role of prolactin in modulating insulin, glucagon and glucose concentrations as well as the possibility that oxytocin affects gastrin and somatostatin levels following weaning are discussed.

Long-acting somatostatin analog controls acid and gastrin secretion in benign, not in malignant, Zollinger-Ellison syndrome.

The long-acting somatostatin (SMS) analog, SMS 201-995 has beneficial effects on APUDomas. In two Zollinger-Ellison syndrome (ZES) patients we assessed basal acid output (BAO) and 24-h pH under SMS and compared them to controls. We also assessed total gastrin, gastrin 17, insulin, glucagon, C-peptide, and SMS by radioimmunoassay. In the benign gastrinoma, an acid-controlling action of SMS was shown, elevating the 24-h pH threshold over the pH range 1.5-5 of 55-10% compared with control. A parallel inhibition of the gastrins greater than 90% was apparent. We found no beneficial effect on gastric acid secretion and on tumor gastrin in the malignant gastrinoma despite a fourfold higher plasma SMS level. Non-tumor-related peptides were suppressed by approximately 50% and in contrast to gastrin they again reached pre-SMS levels before the next dose of the drug. We conclude that SMS is more effective in benign than in malignant gastrinomas, and may be exclusively so.

Effect of somatostatin analogue (SMS 201-995) on molecular species of gastrin in gastrinoma.

Somatostatin analogue (SMS 201-995) has been shown to decrease total serum gastrin in patients with gastrinoma; however, the gastrin level rarely returns to normal, despite the near-complete inhibition of acid secretion. This implies that SMS may have an inhibitory action on the biologically active molecular species of gastrin and have little effect on biologically inactive species. To test this hypothesis, we determined the effect of SMS on the molecular species of gastrin in eight patients with the Zollinger-Ellison syndrome. Serum obtained before treatment and 6 hours and 18 hours after treatment (SMS 1 microgram/kg, subcutaneously) was sampled and assayed for molecular species of gastrin by means of gel filtration chromatography and fractional quantitation of gastrin species by radioimmunoassay. There was a significant decrease in the amount of G-34 and G-17 species. BBG and G-14 decreased, a change not significant at 6 hours but significant 18 hours after SMS. The distribution of the various molecular species as a percent of total immunoreactive gastrin was analyzed before and after SMS. There was a shift in the distribution of the molecular species, so that 6 hours after SMS treatment nearly 50% of total gastrin activity was accounted for by BBG and component I. SMS seems to have a different potency to inhibit release of the various gastrin molecular species. This observation may explain the failure of total gastrin levels to return to normal after SMS treatment in patients with the Zollinger-Ellison syndrome.

Chinchilla “big” and “little” gastrins

Gastrin heptadecapeptides (gastrins I and II which differ in the presence of sulfate on the tyrosine of the latter) have been purified and sequenced from several mammalian species including pig, dog, cat, sheep, cow, human and rat. A 34 amino acid precursor (“big” gastrin), generally accounting for only 5% of total gastrin immunoreactivity, has been purified and sequenced only from the pig, human, dog and goat. Recently we have demonstrated that guinea pig (GP) “little” gastrin is a hexadecapeptide due to a deletion of a glutamic acid in the region 6–9 from its NH 2-terminus and that GP “big” gastrin is a 33 amino acid peptide. The chinchilla, like the GP, is a New World hystricomorph. This report describes the extraction and purification of “little” and “big” gastrins from 31 chinchilla antra. Chinchilla “little” gastrin is a hexadecapeptide with a sequence identical to that of the GP and its “big” gastrin is a 33 amino acid peptide with the following sequence: 〈ELEPQGPPHLGTDLSKKQGPWAEEEAAYGWMDF#

Gastrin release from dispersed gastrinoma cells: Effects of calcium and calcium lonophore (A23187)

Dispersed single-cell suspensions of human gastrinoma tissue were incubated for 15, 60, and 120 min in a calcium-containing medium, (0.1, 2, 10 m M) in calcium-free medium and in calcium-free medium containing the calcium ionophore A23187 (0.01, 1, and 100 μg/ml). Supernatant and pellet (intracellular) gastrin levels were determined by radioimmunoassay. Supernatant gastrin levels remained stable over 120 min in calcium chloride or calcium gluconate containing medium, while intracellular pellet gastrin approximately tripled during the same incubation period. Total gastrin (supernatant plus pellet) approximately doubled during the 2-hr incubation in calcium. However, calcium (0.1, 2, or 10 m M) failed to produce a dose-dependent rise in supernatant, pellet, or total gastrin when compared to calcium-free incubates. Contrary to the expected gastrin response to calcium, supernatant and pellet gastrin levels were higher in incubates in calcium-free medium than in calcium-containing incubates. A23187 (0.01 or 1 mcg/ml) in a calcium-free medium decreased supernatant gastrin while high dose ionophore (100 mcg/ml) increased supernatant gastrin. All doses of ionophore stimulated pellet and total gastrin levels. Thus, it appears that the clinical augmentation of gastrin levels, seen with calcium challenge in vivo may not be solely due to changes in serum calcium.

On the natural history of hypergastrinemia.

We determined total gastrin and pepsinogen I in frozen serum samples from 175 overnight-fasted women 54 years old, and from 81 overnight-fasted women 60 years old, who took part in a population study in 1968-69. We also assayed samples from some of these women, who participated in clinical follow-up studies in 1974-75 and 1980-81: all of the women in the initial group whose serum gastrin concentration exceeded the 85th centile value and, as a reference group, a randomized subsample of women whose initial serum gastrin concentration was less than the 80th centile. Samples with total gastrin concentration greater than 400 ng/L were also assayed for gastrin-17 and gastrin-34. We found that: a pronounced increase of serum gastrin persisted throughout the study period for most of these postmenopausal women, indicating that conversion of type A gastritis (antrum-sparing) to pan-gastritis is uncommon; unexplained high concentrations of pepsinogen I in relation to the reference interval for young and middle-aged adults, as well as in relation to serum gastrin, were common; and the gastrin-17/gastrin-34 ratio is not correlated with the outcome of pronounced hypergastrinemia.