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)

Peptide analogues of the C-terminal tetrapeptide of gastrin in which the phenylalanine had been replaced were synthesized and their biological activity on acid secretion evaluated. Compounds Boc-Trp-Leu-Asp phenylethylamide 6, Boc-beta-Ala-Trp-Leu-Asp phenylethylamide 9, Boc-Trp-Leu-Asp p-fluorophenylethylamide 19, Boc-Trp-psi(CH2NH)-Leu-Asp phenylethylamide 23, Boc-Trp-Leu-Asp 2,2-diphenylethylamide 15, and Boc-D Trp-Leu-Asp 2,2-diphenylethylamide 21, in which the phenylalanine had been replaced by phenylethylamine, p-fluorophenylethylamine or 2,2-diphenylethylamine were synthesized. None of these derivatives showed activity on acid secretion in the anaesthetized rat at doses as high as 5 mg/kg. However, they were potent inhibitors of gastrin-induced acid secretion, with ED50 varying from 0.1 to 0.6 mg/kg.
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PMID:Phenylethylamide derivatives of the C-terminal tetrapeptide of gastrin. Potent inhibitors of gastrin-stimulated acid secretion. 381 70

In an effort to identify and characterize precursors of gastrin in tissues, we generated region-specific antisera against a synthetic progastrin peptide, Try-Gly-Trp-Met-Asp-Phe-Gly-Arg-Arg (GL9), as deduced from the nucleotide sequence of gastrin mRNA. This antisera did not cross-react with gastrin or progastrin peptides with shorter carboxyl-terminal extensions. Progastrin-like immunoreactivity (PGLI) was measured in porcine antrum at a concentration of 6.8 +/- 1.2 pmol/g wet weight (mean +/- SE, n = 5), or roughly 0.2% of that of gastrin. On Sephadex G50 chromatography, a major peak of PGLI was eluted as a slightly larger molecule than gastrin heptadecapeptide (G17) but possessed the same N-terminal immunoreactivity. These findings suggest that G17 may be formed by processing of a carboxyl-terminally extended precursor as an alternative to cleavage of big gastrin (G34).
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PMID:Progastrin-like immunoreactivity in porcine antrum: identification and characterization with region-specific antisera. 383 47

We developed a radioimmunoassay specific for glycine-extended progastrin processing intermediates (G-Gly) using antisera generated against the synthetic peptide Tyr-Gly-Trp-Met-Asp-Phe-Gly. Distribution of immunoreactivity in the porcine gastrointestinal tract obtained with this antibody paralleled that of gastrin with the mucosa containing the highest quantity, 116 +/- 22 pmol/g, wet weight (mean +/- S.E., n = 5), or roughly 4% of gastrin concentration. This immunoreactivity was localized specifically to antral mucosal G-cells by immunohistochemistry. On Sephadex G-50 column chromatography of porcine antral mucosal extracts glycine-extended progastrin processing intermediates were separated into three principal molecular forms, each corresponding to known molecular forms of gastrin, component I, tetratriacontagastrin (G34) and heptadecagastrin (G17). Following purification by antibody-coupled affinity chromatography, one molecular form corresponding to G17 in size was shown to have an amino terminus identical to that of G17. Another molecular form corresponding to G34 in size could be converted to the molecular form corresponding to G17 by tryptic digestion. Our findings indicate that glycine-extended progastrin processing intermediates may serve as immediate precursors for each molecular form of gastrin, thus suggesting an alternative pathway for gastrin biosynthesis more complex than that previously conceived.
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PMID:Identification and characterization of glycine-extended post-translational processing intermediates of progastrin in porcine stomach. 384 Jan 61

The effects of the intragastically administered individual L-amino acids, phenylalanine, tryptophan, glycine, aspartic acid, and leucine on lower esophageal sphincter (LES) pressure and serum gastrin concentration were studied in normal subjects. On separate days and in random, double-blind fashion, 13 adult male subjects received isotonic 0.1 M concentration of amino acids and saline, at pH 5.5 in a volume of 600 ml by rapid intragastric instillation over 5 min. LES pressure and serum gastrin concentration were monitored basally and then at frequent intervals for 90 min. Only tryptophan had a significant effect on LES pressure when compared with saline, decreasing LES pressure from 20 to 60 min after administration (p less than 0.01). Only phenylalanine and tryptophan produced significant stimulation of serum gastrin levels with peak increases above basal occurring 30 min after administration (p less than 0.05). It is concluded that: aspartic acid, leucine and glycine produced no significant changes in LES pressure or serum gastrin level; tryptophan and phenylalanine significantly increased serum gastrin concentration; tryptophan significantly decreased LES pressure whereas phenylalanine had no effect; the mechanism of inhibition of LES pressure by tryptophan is not defined and may be mediated by neural or hormonal pathways possibly involving a duodenal receptor.
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PMID:Effect of intragastric amino acids on lower esophageal sphincter pressure and serum gastrin in man. 395 32

High-resolution 1H nuclear magnetic resonance (NMR) spectroscopy at 300 MHz has been used to study the behavior of human gastrin in aqueous solution. A large number of resonances have been assigned by analysis of one- and two-dimensional NMR spectra and the effects of pH and by comparison with the spectrum of des-less than Glu1-gastrin. In gastrin, the ratio of cis to trans conformations around the Gly-2 to Pro-3 peptide bond is 3:7. This is reflected in splitting of the resonances of several neighboring residues and of a residue distant in the sequence, Tyr-12. The pKa of Tyr-12 is 10.7. Sulfation of this residue perturbs the resonances of Tyr-12 and Gly-13 but has very little effect on the rest of the spectrum. A study of the temperature dependence shows that several perturbed resonances move toward their expected positions as the temperature is raised but with a linear dependence on temperature, consistent with a redistribution of populations among accessible local conformations rather than a cooperative conformational change. Addition of Na+ or Ca2+ causes only minor changes in the spectrum. The paramagnetic metal ion Co2+ produces a number of spectral changes, reflecting strong binding to at least one site involving the Glu residues and weaker binding to Asp-16.
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PMID:High-resolution proton nuclear magnetic resonance studies of human gastrin. 400 24

We have isolated a human gastrin gene from a genomic library by employing a human gastrin cDNA clone as a hybridization probe. The total length of the gene is approximately 4.0 kilobase pairs, and the gene is separated into three exons and two introns. A 130-base-pair intron interrupts the coding region and a 3.0-kilobase-pair intron is located in the 5' untranslated region. Nucleotide sequence analysis showed that all of the exon-intron boundaries follow the A-G/G-T consensus sequences. A putative transcription initiation site is assigned to the adenine 60 nucleotides upstream from the exon-intron junction on the basis of S1 nuclease protection mapping. A possible "TATA" equivalent sequence T-T-A-T-A-A is located 28 base pairs upstream from the transcription initiation site. A "CAT box" sequence, C-A-T-T, is located 99 nucleotides upstream of the transcription initiation site. A poly(A)-addition signal, A-A-U-A-A-A, is located 80 base pairs downstream from the termination codon. Comparison of the nucleotide sequences of the human cDNA and the genomic clone revealed that the aspartic acid codon at position 71 of preprogastrin is interrupted by the small intron (130 base pairs). The 3' region of the large intron contains a sequence of 300 nucleotides that is flanked by 15-nucleotide direct repeats. This sequence exhibits a striking homology to the human Alu-type sequence.
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PMID:Structural analysis of the gene encoding human gastrin: the large intron contains an Alu sequence. 608 40

Cholecystokinin (CCK)-like immunoreactivity (CCK-LI) in a pool of 12 dog brains was extracted sequentially into boiling water and cold 2% trifluoroacetic acid. Gel filtration on Sephadex G-50 revealed three main molecular forms detected by a carboxyl-terminal antibody; one was eluted in the position of CCK-58 (58 amino acid residues long); a second, in the position of CCK-8; and a third, near the radioactive iodide marker. When the CCK-LI was purified by affinity chromatography using carboxyl-terminal CCK antibody followed by three steps of reversed-phase high-pressure liquid chromatography, three components were isolated and characterized by sequence microanalysis. The smallest component was the pentapeptide common to gastrin and CCK. The second peak was eluted in the same region as synthetic CCK octapeptide, and sequence analysis showed that the chemical structure of this biologically active region of canine CCK is identical to that found in sheep and pig brains. The 22-residue amino-terminal sequence of brain CCK-58 was: Ala-Val-Gln-Lys-Val-Asp-Gly-Glu-Pro-Arg-Ala-His-Leu-Gly -Ala-Leu-leu-Ala-Arg-Tyr-Ile-Gln-, the same as the sequence found for canine intestinal CCK-58 from this pool of dogs. This is the same sequence others have reported for porcine brain CCK-58 lacking nine amino acid residues (CCK-58 desnonapeptide) except that the porcine peptide had a serine in position 9. The canine CCK amino-terminal sequence differed from the sequence Ala-Gln-Lys-Val-Asn-Ser previously reported for intestinal CCK-58 purified from another pool of dog tissue, but the rest of the residues identified were identical in the two peptides. CCK-58 may be a molecular precursor of the smaller forms of CCK in brain as well as in gut.
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PMID:Isolation of a large cholecystokinin precursor from canine brain. 609 6

The hexapeptide Z-Tyr(SO-3)-Met-Gly-Trp-Met-Asp-NH2, from the natural sequence of C-terminal cholecystokinin was found to be a competitive antagonist of cholecystokinin receptors, in vitro. In the present study, we report that this peptide inhibits gastrin-induced acid secretion in vivo, (ED50 = 1.5 mumol . kg-1), without agonist activity. Desulfation of the tyrosine residue slightly altered this effect. The tripeptide Boc-Trp-Met-Asp-NH2 showed similar effects, but had lower potency (ED50 = 12 mumol . kg-1). From these preliminary results, it can be concluded that removal of the phenylalanine residue from the C-terminal sequence of CCK or gastrin, leads to an antagonist of the natural hormones and that C-terminal phenylalanine residue is important for agonist activity. As compared with proglumide, a well known gastrin receptor antagonist, these peptides were 20-200 times more potent as inhibitors on the same model.
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PMID:A new class of potent gastrin antagonists. 609 50

In pancreatic islets a peptide corresponding to the C-terminal tetrapeptide amide of cholecystokinin and gastrin, Trp-Met-Asp-Phe-NH2, is present in nerve terminals. This tetrapeptide amide is uniquely potent as a releaser of insulin and the other islet hormones, whereas larger cholecystokinins and gastrins as well as tetrapeptide analogues are considerably less potent. We suggest that neural release of the tetrapeptide amide is implicated in regulation of pancreatic hormone secretion.
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PMID:Neural regulation of pancreatic hormone secretion by the C-terminal tetrapeptide of CCK. 610 7

A general method for the detection and characterization of an mRNA using an oligodeoxynucleotide probe is described. The results presented indicate that a G-dT or a dG-U base pair within a short DNA-RNA hybrid does not significantly reduce the stability of the hybrid. On this basis, we propose that 11 amino acids, including Trp and Met, can be used in selecting a peptide sequence suitable for use in designing an oligodeoxynucleotide probe complementary to a given mRNA. To test this hypothesis, we have synthesized an oligodeoxynucleotide (oligo II) complementary to the region of gastrin mRNA coding for Trp-Met-Asp-Phe and have compared its effectiveness as a hybridization probe and as a primer for the synthesis of gastrin-specific cDNA with another oligonucleotide (oligo I) complementary to the region of gastrin mRNA coding for Trp-Met-Glu-Glu. Unlike oligo I, oligo II functions as a primer in specific cDNA synthesis only when the mRNA is denatured prior to initiation of synthesis. Similarly, oligo II can be used as a specific hybridization probe for gastrin mRNA only when the RNA is denatured and partially cleaved with NaOH before hybridization. A simple procedure for denaturing gastrin mRNA to ensure efficient interaction with oligodeoxynucleotide probes is described. This procedure should be useful in studies with other oligonucleotides and mRNAs as well.
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PMID:A general method for detection and characterization of an mRNA using an oligonucleotide probe. 616 Nov 25


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