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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Analogues of yeast alanyl tRNA with I34 replaced by A34 or G34 were synthesized. Synthetic analogues of yeast alanyl tRNT occupy the same position as the natural yeast alanyl tRNA on polyacrylamide gel electrophoresis, and their purity is about 95% after electrophoresis on a 10% or 20% polyacrylamide gel. The two terminal and nearest neighbour nucleotides of the analogues are all correct. The accepting activity of the synthetic analogues is similar to that of the reconstituted natural yeast alanyl tRNA. The incorporation activity of alanine into proteins of the synthetic analogues is about 30% of that of the natural of reconstituted natural yeast alanyl tRNA when I34 is replaced by A, and is 90% when I34 is replaced by G. The reason of the variation in biological function of the analogues of yeast alanyl tRNA after I34 replaced by A or G was discussed.
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PMID:Biological function of modified nucleotides in tRNA molecules--synthesis and biological activity of the analogues of yeast alanyl tRNA with I34 replaced by A34 or G34. 321 91

There is a potential phosphorylation site in the C-terminal region of the precursor for the acid-stimulating hormone gastrin, which is immediately adjacent to an important cleavage point. In the present study we have sought to identify, separate, quantify and characterize phosphorylated and unphosphorylated forms of human progastrin and its fragments. Identification was made by two radioimmunoassays: (a) a novel assay employing an antibody raised to intact human progastrin; and (b) an assay using antibody reacting with the C-terminal tryptic fragment of human progastrin, as well as progastrin itself. Two forms of human progastrin isolated from a gastrinoma were separated by ion-exchange h.p.l.c., and had similar elution positions on reverse-phase h.p.l.c. and on gel filtration. The more acidic peptide contained close to equimolar amounts of phosphate. On trypsinization, peptides were released that co-eluted on ion-exchange h.p.l.c. with, and had the immunochemical properties of, naturally occurring C-terminal fragments of progastrin. One of the latter was isolated and shown by Edman degradation after derivatization with ethanethiol to have the sequence Ser (P)-Ala-Glu-Asp-Glu-Asn. Similar peptides occur in antral mucosa resected from ulcer patients. The unphosphorylated forms of progastrin predominated, whereas the phosphorylated forms of the C-terminal fragments were predominant. This distribution could be explained by preferential cleavage of phosphorylated progastrin. We conclude that in human progastrin, Ser-96 can occur in the phosphorylated form; this residue immediately follows a pair of basic residues (Arg-Arg) that are cleaved during synthesis of the biologically active product.
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PMID:The human gastrin precursor. Characterization of phosphorylated forms and fragments. 322 64

An antiserum, L221, has been developed that is specific for the C-terminal region of the N-terminal tridecapeptide (i.e., 1-13) fragment of the acid-stimulating hormone, G17. In contrast to N-terminal G17 antisera previously used to estimate 1-13 G17, L221 does not cross-react with other N-terminal gastrin fragments or with C-terminal extensions of G17. Using L221 in conjunction with conventional gastrin antisera, and reversed-phase HPLC, it has been possible to identify in addition to 1-13 G17 a further, formerly unrecognised gastrin fragment, 1-11 G17, in stomach extracts. The production of 1-13 G17, 1-11 G17 and other gastrin forms such as the biologically active hexapeptide G6 which is known to occur naturally cannot be explained by tryptic cleavage of progastrin. Instead, their biosynthesis could be explained by the actions of an enzyme with an endopeptidase 24.11-like specificity. In porcine antrum, unsulphated and sulphated G17 are present in similar amounts, but unsulphated 1-13 G17 was about twice as abundant as sulphate 1-13 G17. This is consistent with previous in vitro findings that endopeptidase 24.11 has a higher affinity for the Ala-11-Tyr-12 and Gly-13-Trp-14 bonds in unsulphated G17, than in sulphated G17. The results suggest a novel albeit minor, processing pathway for gastrin biosynthesis in pig antrum involving an enzyme resembling endopeptidase 24.11.
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PMID:A novel gastrin-processing pathway in mammalian antrum. 336 33

Gastrin biosynthesis involves a complex series of posttranslational modifications; their elucidation requires a knowledge of the structure of the gastrin precursor. The complete structure of rat preprogastrin was deduced from the nucleotide sequence of a full length cDNA clone isolated from a rat antral cDNA library. Northern blot hybridization analysis of rat antral RNA together with human antral RNA, reveals a single mRNA species of approximately 670 bases. Comparison of this sequence with those of porcine and human gastrin reveals extensive (73%) homology in the gastrin coding region as well as short regions of conserved nucleotides in the noncoding regions. The rat sequence encodes a preprogastrin of 104 amino acids which consists of a signal peptide, a 37 amino acid prosegment; and the gastrin 34 sequence, followed by a glycine (the amide donor), and flanked by pairs of arginine residues. Cleavage at an internal pair of lysine residues yields gastrin 17. Unlike the human and porcine sequences, rat preprogastrin contains a 9 amino acid carboxy-terminal extension peptide (-Ser-Ala-Glu-Glu-Glu-Asp-Gln-Tyr-Asn) which is homologous to the midportion of gastrin 17 including the site of tyrosine sulfation.
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PMID:Molecular cloning and sequencing of a rat preprogastrin complementary deoxyribonucleic acid. 345 95

The secondary structures of three gastrin analogs, HC1 X H-Trp-Nle-Asp(O-tBu)-Phe-NH2 (tetragastrin), pGlu-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH2 (octagastrin), and H-Leu-(Glu)5-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH2 (minigastrin) were studied by 1H-n.m.r. in dimethylsulfoxide and in trifluoroethanol. All three compounds were found to assume a random conformation in the former solvent, while some ordered secondary structure is present in trifluoroethanol even at the tetrapeptide level. This was shown by temperature studies and solvent titrations. At least four amide protons were found to be solvent shielded in the longer hormone.
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PMID:Conformational studies on gastrin related peptides by high resolution 1H-n.m.r. 369 83

A peptide that cross-reacted with C-terminal gastrin/CCK antisera was isolated from chicken antral extracts by a combination of gel filtration and reversed-phase HPLC. The sequence was: Phe-Leu-Pro-His- Val-Phe-Ala-Glu-Leu-Ser-Asp-Arg-Lys-Gly-Phe-Val-Gln-Gly-Asn-Gly-Ala- Val-Glu-Ala-Leu-His-Asp-His-Phe-Tyr-Pro-Asp-Trp-Met-Asp-Phe(NH2). Aside from the C-terminal tetrapeptide and the Tyr residue, the molecule does not resemble other known forms of gastrin or CCK. The peptide was a potent stimulus of avian gastric acid but not pancreatic secretion. The results have important implications for the structure-activity and evolutionary relationships of the gastrin/CCK family.
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PMID:Isolation from chicken antrum, and primary amino acid sequence of a novel 36-residue peptide of the gastrin/CCK family. 374 81

A series of phenethyl ester derivative analogues of the C-terminal tetrapeptide of gastrin, in which the phenylalanyl residue has been replaced by a phenethyl group and the peptide bond between aspartic acid and phenylalanine by an ester bond, were synthesized. None of these derivatives were able to stimulate gastric acid secretion in the anesthetized rat, whereas they inhibited gastrin-induced acid secretion with ED50 values between 0.02 and 1.5 mg/kg. Among these derivatives, Boc-beta Ala-Trp-Leu-Asp phenethyl ester (9) and Boc-beta Ala-Trp-Leu-Asp p-fluorophenethyl ester (16) were very potent in inhibiting gastrin-induced acid secretion. From these studies, the significant role of the C-terminal dipeptide of gastrin was pointed out. More particularly, the functional role of the phenylalanine through the C-terminal carboxamide and its binding role through its aromatic ring were demonstrated.
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PMID:Phenethyl ester derivative analogues of the C-terminal tetrapeptide of gastrin as potent gastrin antagonists. 378 82

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

Healthy laboratory dogs appear to absorb a mixed meal from the gut at a constant rate. This rate is apparently not affected by meal size. If this is the case, then duration of absorption should depend on total or integrated meal size, whereas metabolite and hormonal levels would be independent of the number of feedings. To explore these hypotheses further, we compared the metabolite and hormonal responses with a single mixed meal and one divided in two halves, provided in two feedings 4 h apart. We detected no effect of the second meal in the metabolic response levels of glucose, lactate, pyruvate, alanine, free fatty acids, or 3-hydroxybutyrate or the hormonal responses of insulin, pancretic glucagon, gastrin, or secretin. Only minor differences were detectable in the hormonal response levels of pancreatic polypeptide, gastric inhibitory peptide, and enteroglucagon, consistent with a response to a second meal. We conclude that the observed change in circulating metabolite or hormone concentration is independent of the size of meal eaten, but the duration of the excursion depends on meal size. Thus, during the bulk phase of nutrient uptake, the absorption mechanism of the laboratory dog appears to be saturated.
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PMID:How laboratory dogs accommodate meals of different size but similar composition. 403 39

Porcine ileal mucosa was homogenized and freeze-thawed in 0.05 M NH4HCO3 + 0.01 M EDTA + 1 mM benzamidine hydrochloride at pH 8.6. Subsequent stepwise precipitation with (NH4)2SO4 followed by fractionation on Sephadex G-50 medium and G-50 fine eluted with alkaline buffer and final fractionation on G-50 superfine in 1.0 M acetic acid yielded a pure protein of 13,000 daltons as determined by sodium dodecyl sulfate electrophoresis. The amino acid composition of the protein has been determined and it contains 126 residues with no tryptophan detectable. Tryptic peptide maps demonstrate that the protein does not contain glucagon and RIA of the peptide did not detect any immunoreactive glucagon or gastrin. The isoelectric point is 6.4. The intact protein is resistant to Edman degradation and the partial N-terminal sequences of two CNBr fragments are: Lys-Arg-Leu-Ala-Leu ...., Glu-Gly-Gly-Thr-Val-Val-Val-Asn-Ser.... The C-terminal residue, alanine was determined using carboxypeptidase Y. The isolated peptide, in the range of 10(-15)-10(-9) M stimulated oxyntic cell hydroxyl ion production in sections of guinea pig gastric fundus. The dose response was linear with biphasic peaks at 10(-14) and 10(-9) M and the maximal response to the peptide was equal to that observed with gastrin. The addition of either atropine (10(-5) M) or cimetidine (10(-5) M) with the peptide (10(-14) M) caused greater than 50% inhibition of oxyntic cell stimulation (P less than 0.005). This peptide is a potent stimulator of the oxyntic cell and its effect is inhibited by muscarinic cholinergic and H2 receptor blockers. Hence, it represents a significant component of the physiological enterooxyntin effect observed in response to intestinal meals.
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PMID:Isolation and partial characterization of an entero-oxyntin from porcine ileum. 609 Jan 3


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