Forms Of Gastrin Research Articles

Studies with bombesin in man.

AbstractThe bombesin (BBS) infusion test was performed in 232 subjects with a variety of conditions, including 35 normal individuals, 41 duodenal ulcer patients, 13 gastric ulcer patients, and 14 patients with Zollinger‐Ellison syndrome. Side effects occurred in 80% of patients, but in only 6% was the test discontinued due to discomfort. All side effects promptly subsided when BBS infusion was interrupted. The dose of BBS eliciting the maximal gastrin response was 15 ng/kg per minute. In man, BBS showed a powerful stimulatory action on antral and gastrinoma G cells. No effect on duodenal G cells was apparent. Plasma levels of the different molecular forms of gastrin were all augmented by BBS infusion. BBS potentiated the gastrin response to a meal and elicited a prolonged and sustained gastrin response in patients with Menetrier's disease. Cells with BBS‐like immunoreactivity were demonstrated in the gastrointestinal tract of man. These data suggest that BBS may play a physiologic role in man.The clinical value of the BBS test was mainly assessed in the study of patients with postgastrectomy recurrent ulcer. In these patients, the BBS test clearly segregated patients with hypersecretion of gastrin from patients without such hypersecretion, and helped to elucidate the pathophysiologic features causing hypergastrinemia.In perspective, BBS should be viewed as an endocrine polyreleaser (gastrin, CCK, PP, glucagon) and as a member of the family of immunoreactive brain‐gut peptides. The role of BBS in the “brain‐gut axis” remains to be determined.

Cellular origins of different forms of gastrin. The specific immunocytochemical localization of related peptides.

We have localized the antigenic determinants for the main forms of gastrin (big gastrin, G34, and little gastrin, G17) in hog antral mucosa using sequence specific antibodies and an indirect immunofluorescence technique. Populations of monospecific antibodies were obtained after affinity immunoadsorption to remove populations of unwanted specificity. The specificity of the purified antisera was established by direct binding of 125I labeled peptides to antisera at the same dilutions as those used in immunocytochemistry. The results indicate that in hog antral mucosa there is a single population of cells with the antigenic determinants of the C-terminal region of G17 and G34, the N-terminal region of G17, the N-terminal region of G34, and the intact G17 molecule. In duodenum there are cells with only C-terminal reactivity; since gastrin and CCK share a common C-terminal sequence it is concluded that this cell type contains CCK-like peptides rather than gastrin.

Cholecystokinin-like peptides in avian brain and gut

Extracts of turkey brain and jejunum contain a factor closely resembling the COOH-terminal octapeptide of porcine cholecystokinin (CCK). Turkey antral extracts contain factors distinguishable in immunochemical and gel filtration properties from the mammalian forms of gastrin and CCK.

Stimulation of gastric mucosal protein synthesis by different molecular forms of gastrin.

Protein synthesis in gastric mucosa was studied by measuring the incorporation of labeled amino acids into protein by isolated gastric mucosal ribosomes in a cell-free system. In 48-hour fasted rats, administration of the synthetic analogues pentagastrin, tetragastrin and gastrin-17 or naturally occurring molecular forms of human gastrin (G-14, G-34) markedly enhanced (23-123%) the capacity of the gastric mucosal ribosomes to synthesize endogenous mRNA-directed protein in a cell-free system. In the presence of exogenous mRNA (poly-U), the gastric mucosal ribosomes from the saline-treated controls showed a higher poly(U)-directed protein synthesis, compared to each fo the gastrin-treated groups. The protein/polyphenylalanine ratio which represents a ratio of polysomes to monosomes was found increased in ribosomes from the gastrin-treated groups.

The predominanting molecular form of gastrin and cholecystokinin in the gut is a small peptide corresponding to their COOH‐terminal tetrapeptide amide

Acta Physiologica ScandinavicaVolume 105, Issue 1 p. 117-119 The predominanting molecular form of gastrin and cholecystokinin in the gut is a small peptide corresponding to their COOH-terminal tetrapeptide amide JENS F. REHFELD, JENS F. REHFELD Institute of Medical Biochemistry, University of Aarhus, DenmarkSearch for more papers by this authorLARS-INGE LARSSON, LARS-INGE LARSSON Institute of Medical Biochemistry, University of Aarhus, DenmarkSearch for more papers by this author JENS F. REHFELD, JENS F. REHFELD Institute of Medical Biochemistry, University of Aarhus, DenmarkSearch for more papers by this authorLARS-INGE LARSSON, LARS-INGE LARSSON Institute of Medical Biochemistry, University of Aarhus, DenmarkSearch for more papers by this author First published: January 1979 https://doi.org/10.1111/j.1748-1716.1979.tb06320.xCitations: 39AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume105, Issue1January 1979Pages 117-119 RelatedInformation

Immunochemical studies on gastrins in the urine

The concentration and molecular form of gastrin in urine were determined radioimmunochemically. Urine from hypergastrinaemic patients (Zollinger-Ellison syndrome and pernicious anaemia) contained gastrins corresponding to the serum components I and II. The excretion of gastrin increased with increasing gastrin concentrations in serum. Urine from six subjects with normal concentrations of gastrin in serum contained “apparent” gastrin immunoreactivity which could not be removed by specific immunoabsorption. No gastrin was detectable by gel filtration of desalted and concentrated urine from normal subjects. The apparent immunoreactivity was due partly to interference by sodium chloride. The results indicate that hypergastrinaemic patients, in contrast to normal subjects, excrete gastrins in the urine.

Gastrins in cat and dog: evidence for a biosynthetic relationship between the large molecular forms of gastrin and heptadecapeptide gastrin.

1. Extracts of antral, duodenal and jejunal mucosa contained the same concentrations and molecular forms of gastrin in cat and dog. In both species component III constituted 93%, component II 4% and components I and IV each 1% of the total immunoreactivity. 2. During electrical vagal stimulation or feeding in (a) anaesthetized cats with ligated kidney vessels and resected jejunum and ileum, (b) anaesthetized normal cats or (c) conscious normal cats, release of the large molecular forms of gastrin, components I and II, was not detectable. 3. Luminal perfusates of cat antrum contained only component III and occasionally less than 2% of component IV. 4. Intravenous injections into conscious cats of components I, II and III isolated from cat antrum revealed a significantly slower elimination of the large components (t1/2 approximately 4.2 and 4.0 min respectively) than of component III (t1/2 approximately 1.1 min). Thus the absence of components I and II in cat blood cannot be due to rapid degradation. 5. During feeding, components I and II constituted 20% of the total gastrin immunoreactivity in antral venous blood of dogs. This amount is sufficient to account for the predominance of large components in peripheral venous blood in dogs considering their slow metabolic clearance rates. 6. Luminal perfusates of dog antrum contained components I, II and III in proportions corresponding to those found in antrum. 7. The results indicate that components I and II are synthesized in the same proportions in gastrin cells of cat and dog. In the cat, components I and II are, however, never released from the cells. Since these components contain heptadecapeptide gastrin within their sequeaces, they probably represent biosynthetic precursors of the principal gastrin, the heptadecapeptide (component III). The predominance of component III in gastric juice suggests that the feline gastrin cell secretes only component III, which degrades to component IV in blood.

Localisation of gastrins to neuro- and adenohypophysis.

SEVERAL peptides including substance P1,2, somatostatin3,4, the enkephalins5,6 and cholecystokinin (CCK)7–10 have been found both in nerve cells of the brain and in endocrine cells of the gut. CCK was first demonstrated in brain tissue by a gastrin radioimmunoassay as a peptide different from and smaller than heptadecapeptide gastrin7. Using six different gastrin antisera, Dockray provided strong evidence that the reported gastrin immunoreactivity7 corresponded to the COOH-terminal octa-peptide of CCK8, which reacts with certain gastrin antisera because of the identical COOH-terminal pentapeptide sequences of gastrin and CCK. Studies using antisera specific for CCK without cross-reaction with gastrin have now confirmed that CCK is present in large quantities in the brain9,10 and that the peptide originally demonstrated by gastrin antisera7 indeed corresponded to the COOH-terminal octapeptide of CCK. In contrast, no peptides similar to any of the known molecular forms of gastrin have so far been found in brain tissue. We have used various sequence-specific antisera to distinguish between gastrin and CCK, and we report here that true gastrin also is present in the central nervous system. The only region of the brain containing significant amounts of gastrin was the hypophysis cerebri. Both pituitary lobes contained molecular forms of gastrin closely resembling those found in antrum11.

IMMUNOCHEMICAL CHARACTERIZATION OF GASTRIN IN PANCREATIC ISLETS OF NORMAL AND GENETICALLY OBESE MICE

Material with gastrin-like immunoreactivity has been extracted from micro-dissected islets and from antral mucosa of normal and genetically obese mice. The islet and antral extracts cross-reacted with antisera specific for the CO2H-terminal portion of human heptadecapeptide gastrin, but did not cross-react with antisera specific for the NH2-terminal region or with an antiserum specific for the entire, intact, molecule. With the antiserum showing highest cross- reactivity, the concentration of immunoreactive gastrin in normal islet tissue (138 pmol/g, standard human G17-I) was approximately 50% that in obese mouse islets (204 pmol/g) and 2% that in normal antral mucosa (6-1 nmol/g). Following fractionation on Sephadex G-50 the principal forms of gastrin in the islet and antral extracts had similar elution volumes to human heptadecapeptide gastrin, although other, probably smaller, forms of gastrin were also noted in the islet extracts.

Heptadecapeptide Gastrin: Measurement in Blood by Specific Radioimmunoassay

The characteristics are described of an antibody (designated L6) which has virtually absolute specificity for heptadecapeptide gastrin. This antibody binds G17, but does not bind peptide fragments or molecular forms of gastrin comprising G17 with either amino acid deletions, or additions, at the carboxyl- and amino-terminals. In serum from patients with Zollinger-Ellison syndrome the only form of gastrin revealed by L6 was compatible with G17, and there was good agreement between estimated G17 concentrations in serum analyzed by gel filtration and by direct radioimmunoassay using L6. Using L6 in conjunction with antibodies specific for carboxyl- and amino-terminals of G17 it has been possible to measure concentrations of different forms of gastrin in serum of normal subjects after a meal in greater detail than previously possible. After a light meal consisting of eggs, toast, and Oxo, serum concentrations of G17 measured by L6 increased to a peak 20 min after feeding (delta gastrin, 19 pmoles per liter; n = 17). In contrast, concentration of G34 peaked at 50 min (delta gastrin, 27 pmoles per liter). Small amounts of amino-terminal fragments of G17 were present throughout the digestive period. Applying the known ratio of biological potencies of G34 and G17 for stimulation of acid secretion in man, it is estimated that G17 accounts for about 75% of the biological activity in blood after a meal, even though G34 is present in higher molar concentrations.

Immunochemical evidence of cholecystokinin-like peptides in brain.

A NUMBER of peptides including substance P1,2 somatostatin3 and vasoactive intestinal peptide4, have been found both in nerve cells of the brain and gut and in gastrointestinal endocrine-like cells. The biological significance of the occurrence of the same peptides in endocrine and nerve cells is not yet clear, although Pearse has suggested that these cell types might share a common embryological (neuroectodermal) origin5. An antibody to the antral hormone gasrin has recently been shown to cross react with material in extracts of the central nervous system (particularly cerebral hemispheres) of a number of vertebrate species including dog and man6. It is known that in antral mucosa, and in blood, gastrin occurs in several different forms of which the most important are peptides of 17 (G17) and 34 (G34) amino acid residues7. The C-terminal hepta-decapeptide of G34 is identical with G17, and G34 may well be a biosynthetic precursor of G17 (ref. 7). The C-terminal pentapeptide of the two gastrins is also identical with that of the intestinal hormone cholecystokinin (CCK)8, and antibodies specific for the C terminus of gastrin frequently cross react with CCK9. The present study was undertaken to clarify the relationships between the gastrin-like activity in brain and the characteristic forms of gastrin and CCK. We found the distribution of the brain components on Sephadex G-25 to differ from those of previously characterised forms of gastrin and CCK. The pattern of reactivity with different antisera suggests, however, that the brain factors resembled CCK-like peptides more closely than gastrin-like peptides.

Molecular forms of gastrin in antral mucosa, plasma and gastric juice during vagal stimulation of anesthetized cats.

Gastrin was released by electrical vagal stimulation in anesthetized cats. Antral mucosa, blood and gastric juice samples collected during vagal stimulation were subjected to gel filtration in order to characterize the different molecular forms of gastrin. In antral mucosa component III (gastrin-17) predominated. Besides, the antrum contained 5 per cent component II (gastrin-34, "big" gastrin), 1 per cent component I and trace amounts of component IV (gastrin-14 or "mini" gastrin). Immediately after vagal stimulation, component III (gastrin-17) appeared in the gastric venous effluent followed within a few minutes by component IV (gastrin-14). Component I and II (gastrin-34) were not detectable in any of the plasma samples. We suggest that component III (gastrin-17) is released from the antral mucosa and is then rapidly metabolized to component IV (gastrin-14) possibly to a significant extent in the fundic region of the stomach. Large amounts of component III (gastrin-17) were found in the vagally-induced gastric juice. Only very small amounts of degradation products were present, indicating that cat gastrin is relatively resistant to peptic degradation and acid hydrolysis.

The heterogeneity of gastrin, with reference to conversion of gastrin-17.

High-resolution gel chromatography monitored by a sensitive radioimmunoassay for gastrin has disclosed that gastrin circulates in twenty different components. Since the assay is specific for the biological active sequence of gastrin (-Trp-Met-Asp-PheNH2), we conclude that all the twenty circulating molecular forms of gastrin encountered in this study may participate in the regulation of gastric acid secretion. There are two dominating forms of gastrin in serum: gastrin-34-like components and gastrin-17-like components. The former constituted 60% and the latter constitutes approximately 30% of the immunoreactive gastrins. We suggest that extragastrointestinal conversion of gastrin-17, released from tissue, is an important source of gastric-34-like components. Such conversion has been observed in intact man and pig. Studies with the isolated perfused porcine liver indicate that the liver is important in the metabolism of gastrin-17, and that conversion may be a hepatic function.

Effect of secretin on release of heterogeneous forms of gastrin.

The effect of an intravenous injection of secretin on plasma gastrin concentration is shown to be dependent upon the relative concentration of the major forms of immunoreactive gastrin present in the plasma at the time of injection. Secretin suppressed gastrin secretion in the fasting state in patients in whose plasma heptadecapeptide and big gastrins predominated and did not suppress when big big gastrin comprised more than 90% of plasma gastrin immunoreactivity. The post-secretin decrease in plasma gastrin was due entirely to the disappearance of the smaller, more rapidly degraded forms. Food-stimulated gastrin response was suppressed by secretin for the initial 40 minutes after a test meal but was greater than usual from 40 to 120 minutes.

Molecular forms of gastrin in antral mucosa and serum of dogs.

Instillation of liver extract into antral pouches produced an increase in the serum concentrations of both little (G-17) and big (G-34) gastrins. The molar fraction of G-17 plus G-34 represented by G-17 was about 0.9 in antral mucosa and about 0.3 in serum 3 hr after initiating release with liver extract. The predominance of G-34 in serum can be accounted for only in part by its slower rate of removal from the blood so other factors probably also contribute. Although G-17 contributed only about 30% of the total molar concentration of gastrins in serum, it accounted for about 70% of the acid stimulatory activity because on a molar basis it is about five times more bioactive than G-34.

Relative abundance of big and little gastrins in the tumours and blood of patients with the Zollinger Ellison syndrome.

The relative concentrations of big gastrin (G-34) and little gastrin (G-17) were compared in the sera and tumours (gastrinomas) of Zollinger-Ellison syndrome patients. Big and little gastrins were identified in all 10 serum samples and in all 10 tumour biopsies examined. In serum, G-34 (range of concentrations 58-220 000 fmol/ml) was the major form of gastrin and G-17 (22-78 000 fmol/ml) was a minor component; the mean relative abundance of G-17/[G17 + G34]) in serum was 0-18 and the mean relative abundance of G-34 was 0-82. In tumour, however, the opposite was true: G-17 (49-869 000 pmol/g) was the major component and G-34 (45-464 pmol/g) a minor component, and the relative proportions of G-17 and G-34 were 0-73 and 0-27 respectively. Following an intravenous injection of porcine secretin (2-0 U/kg) there was a rapid increase in concentration of all forms of gastrin in the blood, but the increase in G-17 was proportionately greater than that of G-34 (relative abundance of G-17 in basal serum was 0-21 compared with 0-37, five minutes after secretin). Differences in the half lives of G-17 and G-34 may partly explain their relative abundancies in serum and tumour tissue.

Amino Terminal Gastrin Fragment in Serum of Zollinger-Ellison Syndrome Patients

In addition to the previously described molecular forms of gastrin, a new component has been found in high concentrations in the serum of 6 patients with Zollinger-Ellison syndrome. Serum was fractionated by gel filtration, and ion exchange chromatography, and the new component was identified in eluates by radioimmunoassay using an antibody with specificity for the N-terminal portion of heptadecapeptide gastrin. The precise chemical nature of the new component is not known, but its chromatographic behavior and its reactivity to various antibodies is indistinguishable from that of the natural or synthetic N-terminal 1 to 13 fragment of G-17. The new component is present in gastrinoma tumor tissue. Its concentration in serum of gastrinoma patients increases markedly when secretin is injected.

Effect of antrectomy and subsequent vagotomy on the serum gastrin response to food in dogs.

The effect of food on serum gastrin and gastric acid secretion has been studied in dogs with denervated pouches before and after antrectomy and subsequent vagotomy. A Billroth I anastomosis was used in one group of dogs and a Billroth II in the other. Serum gastrin was measured by radioimmunoassay. In both groups of dogs antrectomy significantly depressed mean basal levels of serum gastrin and abolished the rise in serum gastrin in response to a meat meal. Meal-induced pouch acid secretion was considerably lowered by antrectomy after either Billroth I or Billroth II anastomosis. Vagotomy after antrectomy increased basal levels of gastrin, but did not restore the serum gastrin response to a meat meal in either group of dogs. It is suggested that biologically active forms of gastrin are released from the antrum in response to a meal. Biologically inactive basal levels of gastrin apparently originate from extra-antral sources. The post-vagotomy increase in basal (static) gastrin suggests vagal control of the metabolism of static, extra-antral gastrin.

Direct measurement of gastrin release from duodenum and jejunum in dogs.

ARTICLESDirect measurement of gastrin release from duodenum and jejunum in dogsHD Becker, DD Reeder, and JC ThompsonHD Becker, DD Reeder, and JC ThompsonPublished Online:01 Oct 1974https://doi.org/10.1152/ajplegacy.1974.227.4.897MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByEffects of an antral mucosectomy, L-364,718 and atropine on cephalic phase of gastric and pancreatic secretion in dogsGastroenterology, Vol. 98, No. 1Studies of the Release of Gastrin from the Human Duodenum Induced by Gastrin-Releasing Peptide8 July 2009 | Scandinavian Journal of Gastroenterology, Vol. 24, No. 4Effect of Electric Stimulation of the Celiac Vagus on Gastric Acid Secretion and Plasma Concentrations of Somatostatin and Gastrin in the Portal and Gastroepiploic Veins of Dogs8 July 2009 | Scandinavian Journal of Gastroenterology, Vol. 23, No. 9Evidence that bombesin releases extragastric gastrin in manRegulatory Peptides, Vol. 11, No. 1The Type of Anastomosis after Selective Gastric Vagotomy and Precise Antrectomy Is of No Importance for Basal and Postprandial Serum Gastrin Concentration30 April 2018 | Scandinavian Journal of Gastroenterology, Vol. 19, No. 2Contribution of the antrum and duodenum to circulating forms of gastrin in the dogRegulatory Peptides, Vol. 7, No. 2Increase in duodenal tissue gastrin in dogs following antrectomy with gastroduodenostomy and after total gastrectomy with oesophagoduodenostomy 1Acta Physiologica Scandinavica, Vol. 116, No. 2Hormonal Changes After Gastric SurgeryClinics in Gastroenterology, Vol. 9, No. 3Secretin, a stimulus for duodenal and pancreatic “gastrin” release: Possible pathogenetic significance in Zollinger-Ellison (ZE) syndromeJournal of Surgical Research, Vol. 28, No. 4Gastrin cell populations after highly selective vagotomy in the dogThe American Journal of Surgery, Vol. 137, No. 1Einfluß einer Strongyloidesinfektion auf die Bildung von Gastrin und auf andere Hormone beim Schweinl113 May 2010 | Zentralblatt für Veterinärmedizin Reihe B, Vol. 25, No. 9Characteristics of release of duodenal gastrinThe American Journal of Surgery, Vol. 133, No. 3Depletion of antral gastrin after food in ratsThe American Journal of Surgery, Vol. 129, No. 1 More from this issue > Volume 227Issue 4October 1974Pages 897-900 Copyright & PermissionsCopyright © 1974 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1974.227.4.897PubMed4429139History Published online 1 October 1974 Published in print 1 October 1974 Metrics

Renal inactivation of endogenous gastrin in dogs.

Concentrations of gastrin in the renal artery, renal vein, and urine of dogs were determined by radioimmunoassay. Renal blood flow was determined by flowmeters. These measurements allowed calculation of the mass of gastrin lost from blood flowing through the kidney. No loss of gastrin was detected during the basal state or during suppression of endogenous gastrin release by antral acidification. When circulating levels of gastrin were elevated by irrigating the antrum with acetylcholine, a significant mass of gastrin was removed on transit of the kidney. Excretion of gastrin in the urine was minuscule in comparison with the total mass lost. The kidney therefore possesses the power to inactivate stimulated levels of endogenous gastrin. Failure of inactivation of basal levels may be due to a threshold concentration or to a difference in the molecular form of gastrin released on stimulation.