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)

Within the physiological range of other known releasing factors, human pancreatic tumor growth hormone releasing factor (hpGRF) is specific for GH release. Data concerning hpGRF action on cAMP and GH are consistent with the concept of cAMP acting as a second messenger for this releasing factor. hpGRF-stimulated GH release is Ca++ dependent. Exogenous hpGRF40 does not alter the interdigestive gastric motility or secretion of gastrin and motilin in dogs, while large doses of hpGRF stimulate somatostatin release into the hepatic portal blood of the rat. Significant GRF activity as determined by a rat pituitary perifusion system is confined within the median eminence and the arcuate nucleus, though detectable but insignificant GRF activity is present in other area of the hypothalamus and cortex in the rat. GRF activity is present in the ovine brain as well as in the gut. Both tissues contain large (between 4000-5000 daltons) and small (but possibly larger than 1000 daltons) m.w. GRF materials. GRF appears to be structurally different between species and more than one GRF may be present within the same species. One of the ovine brain peptides with GH-releasing activity was partially characterized as His-Ser-Asp-Gly-Ile-Phe-Thr-Asp-Ser-Tyr- Lys-Arg-Try-Asn-Lys-Glu-Met- Ala-Lys--which is similar to rat GRF and porcine VIP having His at the N-terminus. Another peptide with GRF activity which eluted earlier on reverse phase HPLC and later on cation exchange chromatography has also been obtained in a pure form.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone releasing factors in the brain and the gut: chemistry, actions, and localization. 620 12

The effects of sustained fiber ingestion on gastric emptying glucose tolerance, hormone responses, and jejunal absorption of glucose and lysine were studied in healthy volunteers. Subjects were placed on a low-fiber (3 g) diet for 2 wk, followed by 4 wk of an isocaloric diet supplemented with 20 g/day of either apple pectin (7 subjects) or alpha-cellulose (6 subjects). At the conclusion of each dietary period subjects ingested a low-fiber breakfast surface-labeled with 99mtechnetium sulfur-colloid. Gastric emptying half-time, plasma glucose, calcium, phosphorus, insulin, glucagon, gastrin, human pancreatic polypeptide, and motilin were determined. Gastric emptying half-time was prolonged approximately twofold after pectin supplementation (p less than 0.005) and returned to normal 3 wk after discontinuing pectin supplementation. Cellulose supplementation did not alter the gastric emptying rate. Plasma glucose, calcium, phosphorus, and hormonal responses to the meal were unchanged after either pectin or cellulose supplementation. Pectin ingestion did not impair intestinal absorption of glucose or lysine. In contrast to sustained cellulose ingestion, sustained pectin ingestion slows the gastric emptying rate; the mechanism underlying this adaptive effect is unknown.
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PMID:Sustained pectin ingestion delays gastric emptying. 628 2

Antibody specific for the amino-terminal region of cholecystokinin octapeptide (CCK-8) was generated in a highly reproducible way in New Zealand white rabbits by a novel immunization procedure which involves immunization with CCK-8 peptide conjugate coupled with keyhole limpet hemocyanin (KLH) and inhibiting cross-reacting antibody formation by treatment of the animals with a potent tolerogenic conjugate of beta-alanyl-tetragastrin and a copolymer of D-glutamic acid and D-lysine (D-GL). The antisera thus produced specifically react with an amino-terminal region of CCK-8 but not with the non-sulfate form of CCK-8, nor with the carboxy-terminal region which shares a cross-reactive determinant among gastrin and cholecystokinin-related peptides (caerulein, CCK-4, CCK-8, CCK-33 and CCK-39). The antisera produced by this method allowed us to measure specifically CCK in extracts from tissue such as duodenum containing gastrin and CCK at comparable levels.
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PMID:Production of rabbit antibody specific for amino-terminal residues of cholecystokinin octapeptide (CCK-8) by selective suppression of cross-reactive antibody response. 630 Feb 48

In the present study we used the highly sensitive avidin-biotin complex technique (ABC) for detection of gastrin cell (G cell) autoantibodies. Serum samples were studied from 56 patients with histologically proven antral gastritis, 20 adult subjects with histologically proven normal antral and fundal mucosa and from 25 healthy children. The presence of G cell autoantibodies was assessed by both immunofluorescence (IFL) and the ABC-peroxidase method, using sections from paraformaldehyde-lysine-periodate fixed and paraffin embedded human antral mucosa as antigen. Other organ specific and non-organ specific autoantibodies were demonstrated with IFL. Using the ABC method, G cell autoantibodies were found at a dilution of 1:100 in nine of 56 sera with antral gastritis. One of the control sera was positive. The ABC method was considered superior to IFL in demonstrating G cell antibodies, since positively stained G cells could be easily distinguished from the histiocytic cells in lamina propria which sometimes give false positive staining. Furthermore, higher antibody titres results in the ABC method. Thus it is suggested that by analogy to fundal gastritis, some cases of antral gastritis may have autoimmune aetiology.
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PMID:Demonstration of gastrin cell autoantibodies in antral gastritis with avidin-biotin complex antibody technique. 638 22

Various tumor cells contain chromatographically distinct isoacceptor tRNA species. To decide whether the tumor-specific species represent an expression of a separate tRNA gene or only an undermodified form of normal tRNAPhe, nucleotide sequences of tRNAPhe isolated from neuroblastoma and normal mouse liver were determined by postlabeling techniques. The results showed identical sequences except for the changes of post-transcriptional modifications in the anticodon loop. Normal mouse liver tRNAPhe contained Cm32, Gm34, and the hypermodified YOH next to the 3' end of the anticodon. On the contrary, tRNAPhe from neuroblastoma contained C32, G34, and, instead of YOH base m1G. A small proportion of tRNAPhe species contained an undermodified YOH base. For the examination of the conditions leading to the undermodified tRNAPhe, Vero cells derived from the kidney of African green monkey in culture were used. In these cells, deprivation of methionine or lysine resulted in changes in tRNAPhe modification similar to those in tumor cells. Ehrlich ascites tumor cells were examined to determine whether the presence of altered tRNAPhe species in various tumors is also the result of starvation of some nutritional factors. Results obtained with these cells showed that tRNAPhe species lacking the Y base disappeared in tumor-bearing mice after intraperitoneal injection with a mixture of amino acids and vitamins. Thus it is concluded that tumor-specific tRNAPhe species are the products of aberrant post-transcriptional modification, not the transcripts of different, normally repressed genes.
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PMID:Alterations in post-transcriptional modification of the Y base in phenylalanine tRNA from tumor cells. 640 57

Previous studies in our laboratory have shown that substance P (SP), injected into benzylpenicilloyl-keyhole limpet hemocyanin (BPO-KLH) sensitized mice at the peak of the benzylpenicilloyl (BPO)-specific IgE response, suppressed these responses in isotype-specific fashion within 48 h. These studies also showed that SP, but not neurotensin (NT), serotonin (5-HT), somatostatin (SOM) or gastrin, suppressed BPO-specific memory IgE antibody-forming cell (AFC) responses induced in vitro, also in isotype-specific fashion. To investigate the mechanisms by which SP suppressed BPO-specific IgE AFC responses were induced in vitro, these responses were induced by culturing spleen cells from BPO-KLH sensitized mice for 5 days with BPO-KLH with or without whole SP, amino terminal SP (SP 1-4: Arg-Lys-Pro-Lys), or carboxy terminal SP (SP 8-11: Phe-Gly-Leu-Met). In some experiments, the SP receptor antagonist (D-Pro2, D-Phe7, D-Trp9)-SP (D-SP) was included in culture. In other experiments anti-interferon monoclonal antibody (anti-IFN gamma mAb) was in culture. Whole SP and SP 8-11, but not SP 1-4, suppressed BPO-specific IgE AFC responses induced in vitro. The suppression obtained was IgE isotype-specific and dose-dependent. Inclusion of SP receptor antagonist (D-Pro2, D-Phe7, D-Trp9)-SP inhibited suppression of BPO-specific memory IgE AFC responses by SP or SP 8-11. The SP-mediated suppression of BPO-specific memory IgE responses appeared to involve interferon gamma (IFN gamma).
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PMID:Neuropeptide-mediated regulation of hapten-specific IgE responses in mice. II. Mechanisms of substance P-mediated isotype-specific suppression of BPO-specific IgE antibody-forming cell responses induced in vitro. 750 99

We have reported previously mitogenic effects of gastrin on several immortalized and neoplastic cell lines, including Swiss 3T3 fibroblasts. Receptor subtypes, cholecystokinin (CCK)-A and CCK-B, for a closely related peptide, cholecystokinin, were recently cloned. These studies were undertaken to investigate if CCK-A- and CCK-B receptors were perhaps mediating the mitogenic effects of gastrin on Swiss 3T3 cells. Receptor antagonists that inhibit the biological effects and binding of peptides to the CCK-A (L-364,718 (L18)) and CCK-B (L-365,260 (L60)) receptors were ineffective toward inhibiting the binding and proliferative effects of gastrin on Swiss 3T3 cells. Radiolabeled L18 and L60 demonstrated no binding to the cells, indicating that CCK-A and CCK-B receptors may be absent on Swiss 3T3 cells. Radiolabeled CCK-8, gastrin, L18, and L60, on the other hand, demonstrated specific binding to a pancreatic cancer cell line (AR42J cells) (used as a positive control). In cross-linking studies the molecular mass of the major band of gastrin receptors (GR) on Swiss 3T3 cells was determined to be approximately 45 kDa. The mitogenic potency of 0.1-1.0 nM gastrin-like peptides on Swiss 3T3 cells was in the order of G1-17 > or = G1-17-Gly > G5-17 > or = G5-17-Gly > G2-17 > CCK-8-Gly > or = G1-17-Lys > or = CCK-8. The relative binding affinity of the peptides (based on the dose-dependent inhibition of binding of 125I-G1-17 to Swiss 3T3 cells) was similar to the relative mitogenic potency of the peptides as given above. Furthermore, G1-17-Gly was equally effective as G1-17 in displacing the binding of 125I-G1-17 to the 45-kDa GR from the Swiss 3T3 cells. Based on these studies it became evident that the novel gastrin preferring GR, expressed by Swiss 3T3 cells, binds and mediates the mitogenic effects of not only the mature (amidated) forms of gastrin-like peptides but also binds and mediates the mitogenic effects of glycine-extended forms of gastrin-like peptides. Possible mRNA expression of CCK-A and CCK-B receptor subtypes by gastrin-responsive rodent intestinal and fibroblast cell lines (Swiss 3T3, IEC-6, CA) was measured by the methods of Northern blot analysis and reverse transcriptase-polymerase chain reaction. mRNA from rat pancreas, AR42J cells, and rat antrum served as positive controls.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Novel gastrin receptors mediate mitogenic effects of gastrin and processing intermediates of gastrin on Swiss 3T3 fibroblasts. Absence of detectable cholecystokinin (CCK)-A and CCK-B receptors. 772 37

This study was designed to examine whether one or both principle molecular forms of somatostatin (SLI), somatostatin-28 (S-28) and somatostatin-14 (S-14), mediate inhibition of stimulated gastric acid by intestinal fat and to determine whether the mode of action includes activation of type A cholecystokinin (CCK) receptors in conscious dogs. SLI molecular forms were separated by gel filtration chromatography after extraction of acidified plasma on octadecyl silyl cartridges and quantified by RIA. Basal plasma levels of S-28 and S-14 were 4.1 +/- 0.6 and 3.6 +/- 0.3 fmol/ml, respectively. Intraduodenal perfusion with a 10% fat emulsion increased plasma S-28 by 6.3 +/- 1.2 fmol/ml (P < 0.01) and S-14 by 17.8 +/- 2.6 fmol/ml (P < 0.001), and suppressed by 76 +/- 3% (P < 0.001) gastrin (150 pmol/kg.h)-stimulated gastric acid. Blockade of type A CCK receptors with MK-329 (75 micrograms/kg, i.v.) abolished S-28 and S-14 responses (both P < 0.001) and completely reversed the inhibitory effect of gastric acid produced by intraduodenal fat. Intravenous infusions of S-14 dose-dependently inhibited gastrin-stimulated secretion with an estimated 50% inhibitory dose of 125 pmol/kg.h that achieved an incremental plasma S-14 rise of 40 +/- 2 fmol/ml; infusions of S-28 at 30 pmol/kg.h increased plasma S-28 by 47 +/- 3 fmol/ml without altering acid output. The SLI antagonist cyclo-[7-aminoheptanoly-Phe-D-Trp-Lys-Thr(BZL)] (CyCam) reversed by 89 +/- 4% (P < 0.001) exogenous S-14-induced inhibition of gastrin-stimulated acid secretion, but did not influence gastric acid output after the infusion of S-28. CyCam also reversed by 139 +/- 9% (P < 0.001) the early phase of fat-induced acid inhibition; in the late phase, CyCam treatment was associated with a further 2-fold elevation of plasma peptide-YY (PYY) to 102 +/- 6 fmol/ml (P < 0.001) and a 75 +/- 5% suppression of gastric acid. Simulation of this plasma PYY increment with infusions of PYY at 50 pmol/kg.h inhibited by 44 +/- 5% gastrin-stimulated acid secretion. These results indicate that in conscious dogs, endogenous CCK mediation of intraintestinal fat-induced inhibition of stimulated acid secretion occurs in part through CCK type A receptor activation of S-14 secretion. Modulation of gastric acid by S-14 includes both inhibition and attenuation of further suppression via counterregulation of PYY secretion.
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PMID:Cholecystokinin type A receptors mediate intestinal fat-induced inhibition of acid secretion through somatostatin-14 in dogs. 791 Jul 94

The precursor of the acid-stimulating hormone gastrin contains a phosphorylation site which is immediately adjacent to a functionally important cleavage site, and which occurs in a sequence resembling the phosphorylation sites in casein. We have examined phosphorylation of human preprogastrin 93-101 with [gamma-32P]ATP by a Triton-solubilized Golgi membrane preparation from mammary glands of lactating rats. The activity of solubilized Golgi membranes was approx. an order of magnitude greater than that of intact vesicles suggesting a luminal orientation of the kinase. Incorporation of 32P was linear for up to 12 min at 30 degrees C, and the half-maximal rate of phosphorylation at 1 mM ATP was observed at peptide concentrations of 0.2 mM. The Km for ATP was 0.12 mM and the maximal velocity was 2.17 nmol of peptide per min per mg Golgi protein. Proteinase inhibitors (leupeptin, pepstatin, benzamidine) and p-nitrophenyl phosphate did not influence phosphorylation. The incorporation of 32P was inhibited by poly-L-lysine but not by heparin. We conclude that the phosphorylation site in progastrin is a substrate for a Golgi membrane kinase and that a similar enzyme might act on endogenous progastrin in vivo.
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PMID:Phosphorylation of human preprogastrin 93-101 by a Golgi membrane kinase from rat mammary gland. 814 83

We made a mutated progastrin cDNA construct that contains a cleavage site (-Arg(-4)-Arg(-3)-Lys(-2)-Arg-1) specific for the Kex2-like endoprotease furin, located ahead of the bioactive gastrin. For expressing the mutated progastrin cDNA, we used two non-endocrine cell lines, CHO and COS-7. CHO cells exhibit amidating enzyme activity and levels of amidation enzyme mRNA as high as those in the pituitary-derived endocrine cell line GH3, whereas COS-7 cells have far less amidating activity and lower amounts of mRNA. Mutant progastrin-expressing CHO cells produced mostly amidated gastrin. Gel filtration showed the size of this gastrin corresponded to that of the synthetic human gastrin-17. In contrast, COS-7 cells produced glycine-extended gastrin and only a small amount of amidated gastrin. The difference in the amount of amidated gastrin products produced by the two non-endocrine cell lines is due to differing amounts of the amidation enzyme contained in each cell line.
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PMID:Production of bioactive gastrin from the non-endocrine cell lines CHO and COS-7. 827 7


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