Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study evaluates the structure-function relationships of the C-terminal peptide fragments of gastrin and cholecystokinin (CCK) in the biliary system and the stomach. Dogs with chronic biliary and gastric fistulas were used. Administration of the common fragments of CCK and gastrin with four and five amino acids and the active fragments of CCK with six through eight amino acids without sulfation of tyrosine in position 7 failed to alter hepatic bile flow from control values while significantly stimulating gastric hydrogen ion output. Administration of the seven and eight amino acid peptide fragments of CCK with sulfation of tyrosine in position 7 significantly increased hepatic bile flow. Administration of the sulfated octapeptide with 4 microgram/kg per h of nonsulfated octapeptide did not result in the inhibition of the choleresis produced by the sulfated peptide. The gastric hydrogen ion response produced by the administration of the nonsulfated and sulfated peptide was equal to that of the nonsulfated peptide alone. These results suggest that in the biliary system the receptor is highly specific as sulfation of the peptide fragment of CCK is essential for combining with the receptor, whereas in the stomach the receptor has little specificity and combines with all of the peptide fragments evaluated.
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PMID:Structure-function relationships of peptide fragments of gastrin and cholecystokinin. 19 74

Three antisera to the C-terminally extended form of gastrin or the C-terminal flanking peptide of progastrin were used in an attempt to investigate the post-translational processing of progastrin at the cellular level by light and electron microscopical immunocytochemistry. In the normal human gastric antrum, the G-cell secretory granules were found to contain both gastrin and the C-terminal progastrin determinants (progastrin 87-93, 87-95 and 93-101). Immunostaining of serial sections at the light microscopical level revealed that duodenal gastrin-containing cells also express the C-terminal progastrin determinants, as well as gastrin-34. In foetal tissue, cells containing C-terminal gastrin and the C-flanking peptide of progastrin were first seen at 8 weeks of gestation, in the duodenum. They were not found in the stomach until the 11th week. In hyperplastic G-cells and in gastrin-producing tumour cells, the level of C-terminal peptide immunoreactivity was variable and often lower than that seen in normal antrum and only minimal immunoreactivity could be detected using electron immunocytochemistry. This was interpreted as representing altered post-translational processing of progastrin in modified G-cells.
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PMID:Expression of the C-terminal flanking peptide of human progastrin in human gastroduodenal mucosa, G-cell hyperplasia and islet cell tumours producing gastrin. 284 May 76

Big gastrin comprising 34 amino acid residues (G34) consists of an N-terminal pentadecapeptide linked via two lysine residues to a C-terminal heptadecapeptide identical with little gastrin (G17). Both G17 and G34 have now been established as the principal active forms of gastrin. In this study, release of G34 N-terminal peptide fragment of methacholine and porcine gastrin releasing peptide (pGRP) stimulation in isolated rat stomach perfusion system was investigated by radioimmunoassay with use of an antiserum specific to the N-terminal portion of G34. G34 N-terminal immunoreactivity (IR-G34-N) was detected in rat stomach and proximal duodenum, and the highest concentration was found in extract of the antral mucosa. The concentration of IR-G34-N was constantly lower than that of IR-G17. By gel-filtration study, IR-G34-N in antral mucosa extract was attributed mostly to the G34 N-terminal pentadecapeptide-like component, and the concentration of G34 was about one tenth of G17. Methacholine 10(-8)-10(-3) M produced a biphasic dose-dependent release of IR-G34-N from the vascularly perfused isolated rat stomach. The maximal release was shown by 10(-5) M of methacholine. The release was concomitant with that of IR-G17 during methacholine stimulation. Stimulation of pGRP (14-27) (10(-7) M) produced a monophasic release of IR-G34-N from the vascularly perfused isolated rat stomach. The release was concomitant with that of G17 during the stimulation. The integrated IR-G34-N release was not stoichiometric with that of IR-G17, and IR-G34-N was constantly low. Gel-filtration of the perfusate from rat stomach revealed the presence of the G34 N-terminal pentadecapeptide-like component as a sole major component. The present results demonstrate that post-translational processing of the gastrin precursor in the rat antrum did not necessarily produce G34, which is further converted in the tissue to G17-related peptide(s) and that the G34 N-terminal fragment formed in the G34 conversion is stored and released concomitantly with G17-related peptide(s).
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PMID:[Co-existence and co-release of gastrin 34 N-terminal fragment with gastrin 17 in rat stomach]. 306 41

A series of C-terminal peptide segments of gastrin, i.e., (tert-butyloxycarbonyl)-L-tryptophyl-L-methionyl-L-aspartic acid amide, (tert-butyloxycarbonyl)-glycyl-L-tryptophyl-L-methionyl-L-aspartic acid amide, (tert-butyloxy-carbonyl)-L-tyrosyl-glycyl-L-tryptophyl-L-methionyl-L-asp artic acid amide, and (benzyloxycarbonyl)-L-glutamyl-L-alanyl-L-tyrosyl-glycyl-L-tryptophyl-L -methionyl-L-aspartic acid amide were prepared and were shown to competitively inhibit the binding of labeled human gastrin to its receptors in an isolated gastric mucosal cell preparation and to antagonize the action of gastrin on gastric acid secretion (ED50 from 1.5 to 7 mg/kg) in vivo in the reperfused rat stomach, determined according to the method of Ghosh and Schild. From these studies, it could be concluded that the C-terminal phenylalanine residue, which is of primary importance for intrinsic biological gastrin-like activity, is not essential for binding to gastrin receptors.
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PMID:Synthesis and biological activity of new peptide segments of gastrin exhibiting gastrin antagonist property. 609 10

A genomic clone that contains the human gastrin gene was isolated from a human gene library. Restriction endonuclease mapping and DNA sequencing analysis revealed that this gene is about 0.7 kb long, and has an intron. The intron is located at a position that separates the coding region into the peptide region essential for biological activities of gastrin and the non-essential, N-terminal peptide region.
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PMID:Molecular cloning of the human gastrin gene. 632 77

Energy optimizations were performed on some typical conformations of the gastrin C-terminal peptide amide NAc-Trp-Met-Asp-Phe-NH2. Two families of lowest energy conformations were found corresponding to: (a) alpha-helical structures; (b) conformations having beta-structure at the level of Trp residue, and C7-structure at the level of Asp residue. The two aromatic rings were folded on the peptide backbone and ca. 5 A distant from each other (centre to centre). The last family, favoured by energy and population probability, can better account for conformational experimental results and biological activity observations.
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PMID:Conformational calculations on gastrin C-terminal tetrapeptide. 730 51

1. Inhibition of gastric acid secretion by proton pump inhibitors like omeprazole increases the synthesis and secretion of the pyloric antral hormone gastrin. We report here how omeprazole influences the conversion of the gastrin precursor to its final products, and the abundance of mRNAs encoding proteins associated with progastrin processing in rat antral mucosa. 2. Progastrin processing was studied using a pulse-chase protocol in antral mucosa, incubated in vitro, from rats treated with omeprazole for up to 5 days. Labelled peptides were detected by on-line scintillation counting after immunoprecipitation and HPLC. The mRNAs encoding prohormone-processing enzymes were identified by Northern blot, polymerase chain reaction or ribonuclease protection assay, and their cellular origins identified by immunocytochemistry. 3. Cleavage of [3H]- and [35S]-labelled progastrins at Arg-94-95 or Arg-57-58, and amidation at Phe-92 were not influenced by pretreatment with omeprazole. In contrast, cleavage of G34 (the thirty-four amino acid amidated gastrin) at Lys-74-75 to give G17 (the seventeen amino acid amidated gastrin), and of G34-Gly to G17-Gly (G34 and G17 with COOH-terminal glycine), was increased 3-fold after treatment with omeprazole for either 1 or 5 days. 4. Approximately 20% of newly synthesized amidated and Gly-extended gastrins were secreted within 240 min of the labelling period in omeprazole-treated samples, but secretion of labelled gastrins from control tissue was undetectable over a comparable period. 5. The amidating enzyme, peptidyglycine alpha-amidating mono-oxygenase (PAM), the prohormone convertases PC1/3, PC2, PC5 and the PC2 chaperone 7B2 were localized to rat antral gastrin cells by immunocytochemistry. The relative abundance of mRNA species encoding 7B2, PC5 and PAM were unchanged after treatment with omeprazole for 5 days, whereas gastrin, PC1/3 and PC2 mRNAs are known to increase at this time. 6. The main consequence of increased cleavage at Lys-74-75 is the production of G17 and G17-Gly at the expense of G34 and G34-Gly, respectively. The latter have longer plasma half-lives, and so their increased cleavage may serve to limit the rise in plasma gastrin concentration after inhibition of acid secretion. Changes in the abundance of mRNAs encoding prohormone-processing enzymes cannot account for the rapidity of the changes in cleavage of progastrin at Lys residues after omeprazole.
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PMID:Regulation by gastric acid of the processing of progastrin-derived peptides in rat antral mucosa. 926 20

Small cell lung cancer (SCLC) cell lines produce and secrete various peptide hormones, e.g. bombesin (BN)/gastrin releasing peptide (GRP) like peptides that are proposed to function as their autocrine growth factors. To inhibit the proliferative effect of these hormones we have synthesized short chain BN[7-14]-analogues replacing the C-terminal peptide bond by a methylene-amino (-CH2NH-) unit and introducing D-Phe or D-Ser into position 12. As several substance P (SP) analogues were found to inhibit the growth of SCLC cells, some short chain SP-analogues have been synthesized. (Pseudo)octapeptides were synthesized in solution, by fragment condensation using the DCC/HOPfp method. Fragments and SP-analogues were synthesized stepwise using pentafluorophenyl esters. The resistance to hydrolysis of the reduced peptide bond made permitted exact quantification of the Leupsi(CH2NH)Leu pseudopeptide in hydrolysates. The binding ability of both types of peptides to BN-receptors on Swiss 3T3 mouse fibroblast cells and their antiproliferative effect on NCI-H69 human SCLC cell line have been tested and compared with a short chain SP-antagonist pHOPA-D-Trp-Phe-D-Trp-Leu-Leu-NH2 (R) previously described as a potent inhibitor of SCLC proliferation. While BN-analogues showed weak activity in inhibition of proliferation of SCLC cells, SP-analogues 6: D-MePhe-D-Trp-Phe-D-Trp-Leu(psi)(CH2NH)-Leu-NH2 and 7: D-MePhe-DTrp-Phe-D-Trp-Leu-MPA, in spite of greatly diminished affinity towards the BN-receptor, inhibited SCLC proliferation more effectively than R (6: IC50 = 2 microM, 7: IC50 = 5 microM and R: IC50 = 10 microM). Moreover, 6 inhibited the respiratory activity of SK-MES 1 epithelial type of lung carcinoma cells in proliferating but not in the quiescent state, suggesting that the antiproliferative effect of these compounds is not due to simple cytotoxicity. These short chain analogues of SP might be promising candidates as therapeutic agents in the treatment of SCLC.
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PMID:Synthesis of peptide and pseudopeptide amides inhibiting the proliferation of small cell and epithelial types of lung carcinoma cells. 992 55

Cellular synthesis of neuroendocrine peptides requires prohormone convertases (PCs). In order to determine the role of PC2 for gastrin synthesis, we examined antral extracts from mice lacking PC2 or its chaperone, 7B2. The overall concentrations of precursors and alpha-amidated gastrins were similar in all mice. Chromatography, however, revealed that while the K(53)-K(54) site was almost fully cleaved in controls and half cleaved in PC2 null mice, only 23% was cleaved in 7B2 null mice. The results show that PC2 and 7B2 both are required for synthesis of the main form of gastrin (gastrin-17), and that 7B2 exhibits effects beyond PC2-mediated cleavages.
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PMID:Progastrin processing differs in 7B2 and PC2 knockout animals: a role for 7B2 independent of action on PC2. 1175 37