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)

CCK-octapeptide (CCK-8) (EC50 = 0.5 nM), in the presence of Li+, increased 3H-inositol phosphate (IP) accumulation in guinea pig gastric glands prelabeled with 3H-inositol. CCK-8 desulfate, human gastrin I and pentagastrin were much less potent than CCK-8. Antagonists of CCK receptors such as proglumide, dibutyryl-c-GMP and CBZ-Tyr (SO3H)-Met-Gly-Trp-Met-AspNH2 shifted the CCK dose response curve to the right. However, histamine (H1 and H2), cholinergic, substance P and alpha- and beta-adrenergic receptor antagonists had no effect on 3H-IP accumulation induced by CCK. The results suggest that CCK receptor activation in gastric glands leads to an enhanced breakdown of inositol phospholipids which may relate to calcium mobilization and pepsinogen secretion.
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PMID:Cholecystokinin receptor mediated hydrolysis of inositol phospholipids in guinea pig gastric glands. 298 60

The synthesis of the hexapeptide Z-Tyr(SO-3)-Met-Gly-Trp-Met-Asp-NH2, representing the C-terminal sequence of cholecystokinin minus the C-terminal phenylalanyl residue is described. This peptide was shown to be the most potent cholecystokinin receptor antagonist in vitro described to date. It is also able to inhibit gastrin-induced acid secretion in vivo, in the rat and was proved to antagonize the action of the C-terminal octapeptide of cholecystokinin in the central nervous system.
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PMID:Synthesis of Z-CCK-27-32-NH2, Z-Tyr(SO-3)-Met-Gly-Trp-Met-Asp-NH2, a cholecystokinin receptor antagonist and an inhibitor of gastrin-induced acid secretion. 299 59

An extensive array of nerve fibers ramify around the afferent blood vessels of the liver and the extrahepatic and intrahepatic biliary pathways, and are thought to be involved in regulation of blood flow. Although the role of sympathetic innervation is established, little is known about the location or role of regulatory peptidergic innervation in the liver. We examined the anatomic distribution of a wide variety of regulatory peptides and several neural antigens by in situ immunohistochemistry in the rat and in man. A rich peptidergic plexus of nerve fibers and ganglion cells was observed around the arterial vessels in both species, with intense immunoreactivity for neuron-specific enolase, neurofilaments, neuropeptide Y, substance P, and vasoactive intestinal polypeptide. S-100 protein immunoreactivity was seen principally in large nerve bundles, suggesting that the majority of nerves in this area were unmyelinated. In contrast, the portal vessels revealed very little peptidergic innervation. No staining was observed with antibodies directed against insulin, glucagon, gastrin, serotonin, met-enkephalin-Arg-Gly-Leu, cholecystokinin, or growth hormone. These findings indicate the presence of a rich, although selective, peptidergic plexus surrounding afferent hepatic blood vessels. This plexus may play an important role in regulation of hepatic blood flow.
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PMID:Neuroendocrine innervation of the hepatic vessels in the rat and in man. 318 22

Glycine-extended gastrin, the immediate precursor of bioactive (i.e., carboxyamidated) gastrin, was recently identified in antral tissue and in peripheral blood. Studies on pituitary cell lines have shown that although only bioactive peptides are released along the regulated pathway, i.e., stored at high concentrations in secretory granules and released upon appropriate stimulation, the release of precursors is constitutive, i.e., secreted continuously without secretagogue stimulation. To determine whether the secretion of glycine-extended gastrin from the antral G-cell is regulated, meal-induced release was examined. In anesthetized pigs (n = 8) the antral veins were catheterized and blood was collected continuously before and after intragastric instillation of meat extract. Surgical biopsies of antral mucosa were obtained from six animals. Glycine-extended and amidated gastrins were measured and characterized by radioimmunoanalysis and chromatography. The results demonstrate that glycine-extended gastrin is released in a regulated manner from antral G-cells and furthermore the component pattern is identical in mucosa and blood.
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PMID:Corelease of amidated and glycine-extended antral gastrins after a meal. 318 54

To examine the ontogeny of gastrin synthesis and posttranslational processing mechanisms, we utilized region-specific antisera to determine the factors that regulate the contents of gastrin and its precursors in the stomachs of developing rats. Gastrin content increased gradually from birth to a peak at 5 wk of age, after which there was a slight decrease to levels observed in mature animals. Unlike gastrin, glycine-extended precursors of gastrin (G-Gly) increased abruptly in the first day of life but thereafter increased at a steady state. Dexamethasone treatment and early weaning (at 11 days of age) rapidly increased gastrin content, whereas G-Gly content was decreased. On weaning animals to adult rat chow abruptly at an age (18 days) when the corticosteroid surge associated with the weaning process had already occurred, evidence for increases in both gastrin and G-Gly content were observed 7 days later. In contrast, administration of dexamethasone to 18-day-old rats enhanced gastrin content to a greater extent than G-Gly. These results suggest that the natural surge in corticosteroids associated with weaning may enhance gastrin amidation activity, whereas the concomitant dietary changes may exert a stimulatory effect of gastrin synthesis.
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PMID:Development of gastrin synthesis and posttranslational processing mechanisms in rats. 333 38

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

The degradation of human unsulfated heptadecapeptide gastrin (G-17) by human kidney endopeptidase 24.11 has been studied in vitro, and some of the products of degradation have been identified in plasma after in vivo infusion of G-17. The enzyme cleaved G-17 at four peptide bonds: Trp4Leu5, Ala11Tyr12, Gly13Trp14, and Asp16Phe17. The cleavage at Gly-Trp was rapid and 1-13 G-17 was an important intermediate. All the products of cleavage of synthetic 1-13 G-17 were also found after degradation of intact G-17. When normal human volunteers received infusions of G-17, there appeared in their blood peptides with the properties of 1-11, 1-13, 1-16, and 5-17 G-17 on the basis of immunochemical and high-performance liquid chromatographic properties. These observations provide evidence that endopeptidase 24.11 is involved in gastrin metabolism in humans, and may be responsible for the generation of G-17 fragments in the peripheral circulation.
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PMID:In vitro and in vivo degradation of human gastrin by endopeptidase 24.11. 342 7

Recently, glycine-extended processing intermediates of progastrin were identified in porcine stomach using a radioimmunoassay with conventional polyclonal antisera developed against a synthetic peptide analogue for progastrin processing intermediates, gastrin 6-G(Tyr-Gly-Trp-Met-Asp-Phe-Gly). We developed monoclonal antibodies specific for glycine-extended processing intermediates of progastrin (gastrin G). Monoclonal antibody 109-21 appeared to require the carboxyl-terminal pentapeptide structure of gastrin 6-G for maximal binding. Cross-reactivities of 109-21 against gastrin 17 I, gastrin 17 II, cholecystokinin-octapeptide, des(SO3) cholecystokinin-octapeptide, and gastrin 6-G-R-R were respectively 1%, less than 0.1%, less than 0.1%, 0.1%, and 0.5%. With this monoclonal antibody and a polyclonal gastrin antibody we examined the concentrations of gastrin and gastrin G in tissue and the effects of bombesin on the release of gastrin and gastrin G from rat antral mucosa in tissue culture. The gastrin G to gastrin ratio was 2.2 in rat antral mucosa and 0.66 in rat duodenal mucosa. In tissue culture, bombesin significantly stimulated gastrin and gastrin-G secretion at doses of 10(-8) and 3 X 10(-8) M. Atropine (10(-6) M) abolished the actions of carbachol to stimulate gastrin and gastrin-G secretion but had no effect on bombesin-stimulated gastrin and gastrin-G secretion. These results suggest that gastrin G is cosecreted with gastrin in response to carbachol and bombesin, and the stimulation of gastrin and gastrin-G secretion by bombesin does not involve cholinergic neural pathways and may reflect a direct action on gastrin cells.
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PMID:Effects of bombesin on the release of glycine-extended progastrin (gastrin G) in rat antral tissue culture. 359 69

Using radioimmunoassays for amidated and glycine-extended gastrin before and after trypsin-carboxypeptidase B cleavage and chromatography, alpha-carboxyamidation of porcine antral progastrin has been related to tyrosine-O-sulfation and proteolytic cleavages. Corresponding to the sequence at the proteolysis and amidation site, -Gly-Arg-Arg-, antrum contained three COOH-terminally extended precursor types. The glycine-extended gastrins were present in the highest concentrations (241 +/- 58 pmol/g). The degree of tyrosine-O-sulfation was identical for amidated and precursor gastrins irrespective of component size, whereas the component size differed for glycine-extended and amidated forms. For instance, gastrin-34-Gly constituted 54% of the glycine-extended gastrins, while gastrin-34 comprised 8% of the amidated gastrins. The results indicate that tyrosine-O-sulfation occurs prior to NH2-terminal cleavages, which again precede carboxyamidation; but a significant correlation between tyrosine-O-sulfation and proteolytic cleavages or alpha-carboxy-amidation of antral gastrin could not be demonstrated. Furthermore, our results suggest that the immediate precursor of the principal hormonal form, gastrin-17, is gastrin-17-Gly rather than gastrin-34 as previously believed.
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PMID:Alpha-carboxyamidation of antral progastrin. Relation to other post-translational modifications. 368 Feb 81

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


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