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)

The homology screening approach has been used to clone a new member of the guanine-nucleotide-binding-protein-coupled receptor superfamily from guinea pig uterus. The cloned cDNA encodes a 399-amino-acid protein and shows the highest amino acid similarity to members of the bombesin receptor family; 52% and 47% similarity to the gastrin-releasing-peptide (GRP) receptor and the neuromedin-B receptor, respectively. Binding experiments with the stably transfected LLC-PK1 cell line expressing the new receptor protein confirmed the bombesin-like nature of the cloned receptor. The relative order of ligand affinity, GRP = neuromedin C much greater than neuromedin B, suggests that the cloned cDNA represents the GRP subtype rather than the neuromedin-B subtype of bombesin receptors. Northern-blot analysis of mRNA species from several guinea-pig tissues showed that the mRNA for the new bombesin receptor subtype is expressed mainly in uteri of pregnant animals.
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PMID:Molecular cloning of a new bombesin receptor subtype expressed in uterus during pregnancy. 132 7

Various peptide derivatives of the C-terminal decapeptide of gastrin releasing peptide (GRP-10) and neuromedin B (NMB), i.e., carboxyl terminal fragments, amino terminal fragments and substituted analogues, were chemically synthesized and the structure-activity relationships of the peptides were investigated by comparing their contractile activities on the rat uterus. Peptides with chain lengths of 8 and 9 amino acid residues from the C-terminus of GRP-10 and NMB, respectively, had considerable contractile activities. At position 6 of both decapeptides, Val seems to be more favourable than Thr for inducing contraction of the rat uterus. The substitution of His at position 3 and Leu at position 9 of GRP-10 by Leu and Phe, as in NMB leads to a decrease in activity. Moreover, Trp at position 4 and -Met-NH2 at the C-terminus are essential for activity. Furthermore, in order to characterize the bombesin-receptor profile of rat uterus, the inhibitory effect of two peptide antagonists, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P and [Leu13-phi (CH2NH)-Leu14]-bombesin on the contraction of rat uterus were examined.
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PMID:Structure-activity relationships of mammalian bombesin-like neuropeptides in the contraction of rat uterus. 192 98

The localization of peptide hormones and serotonin in ovarian mucinous and endometrioid tumors with argyrophil cells was examined by immunohistochemistry. All of the 15 mucinous tumors had argyrophil cells which resemble the enterochromaffin cells seen in the gastrointestinal tract, and peptide hormones such as gastrin and somatostatin were found in 3 of 5 benign, in 3 of 5 borderline, and in all of 5 malignant tumors. Serotonin was found in 4 benign, 3 borderline and 2 malignant tumors. Of 19 endometrioid adenocarcinomas, type I argyrophil cells which resemble enterochromaffin cells were found in 4 tumors, type II argyrophil cells which contain argyrophil granules mainly in the apical portion or throughout the whole cytoplasm were found in 14, and mixed type cells were found in one. Somatostatin-positive cells were found only in type I cells of a tumor with mixed type argyrophil cells. Serotonin-positive cells were found in 3 tumors containing type I cells. The results obtained were discussed in the comparison with those of cervical and endometrial adenocarcinomas of the uterus. In conclusion, the present study suggests that type I or similar argyrophil cells in ovarian tumors may have endocrine activity.
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PMID:[Immunohistological demonstration of peptide hormones and serotonin in ovarian mucinous and endometrioid tumors with argyrophil cells]. 287 Nov 19

N,N-Dimethyl-N'-(2-diisopropylaminoethyl)-N-(4,6-dimethyl-2-pyridyl)urea (L-634,366) was selected from a series of pyridylurea compounds with antisecretory activity as a potential therapeutic agent for the treatment of ulcer disease. L-634,366 was an effective inhibitor of gastric secretion evoked by gastrin, histamine and 2-desoxy-D-glucose (2-DG) in conscious dogs. Orally, L-634,366 was slightly less potent than the reference H2 receptor blocker, cimetidine as an inhibitor of secretion evoked by histamine, but was equipotent as an inhibitor of secretion evoked by gastrin and 2-DG. In vitro L-634,366 was a weak antagonist of histamine (H2) receptor responses in the guinea-pig atria and rat uterus; in the atria the antagonism appeared to be noncompetitive. In the anesthetized dog, L-634,366 possessed weak anticholinergic activity as compared to atropine in reducing vagally mediated cardiovascular, antral motor responses and with regard to antagonizing the pressor response to the muscarinic stimulant, McN 343-A. The anticholinergic activity of L-634,366 was lower and more selective than that of pirenzepine or atropine in producing mydriasis in mice, in antagonizing acetylcholine induced bradycardia in guinea-pig atria, methacholine and acetylcholine elicited contractions in the guinea-pig ileum and QNB binding to muscarinic receptors. L-634,366, like carbenoxolone, increased incorporation of 3H-glucosamine in gastric mucous indicating an increase in synthesis or turnover of mucous. L-634,366 is a novel compound possessing a broad spectrum of antisecretory activity; in vitro studies suggested a weak noncompetitive inhibition of the histamine-H2 receptor in atria.
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PMID:Gastric antisecretory and pharmacologic properties of N,N-dimethyl-N'-(2-diisopropylaminoethyl)-N-(4,6-dimethyl-2-pyridyl)ur ea (L-634,366). 287 93

1. Frozen and paraffin sections of six species of trematodes: Schistosoma mansoni, S. mattheei, S. japonicum, Schistosomatium douthitti, Echinostoma paraensei and Fasciola hepatica have been incubated with antisera against leu-enkephalin, FMRF-amide, gastrin-17, luteinizing hormone releasing hormone, neurotensin, oxytocin, prolactin, substance P, thyroid stimulating hormone and cholecystokinin, using indirect immunofluorescence and biotin-avidin horseradish peroxidase detection systems. 2. Of the ten antisera tested, six (leu-enkephalin, FMRF-amide, gastrin-17, luteinizing hormone releasing hormone, substance P and cholecystokinin) showed significant immunoreactivity, primarily in the central and peripheral nervous system, and also perhaps in the osmoregulatory system of the three species of Schistosoma. 3. Immunopositive nerve fibers extended from ganglia to gut wall, uterus and vitelline follicles, and especially from subtegumental nerve plexi to sensory receptors on the surface or in dorsal nippled tubercles.
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PMID:Immunocytochemical localization of regulatory peptides in six species of trematode parasites. 290 70

From a side fraction obtained in our previous isolation of neuromedin B from porcine spinal cord, we have purified another decapeptide that exhibits a potent stimulant effect on the smooth muscle preparation of rat uterus. By microsequencing and synthesis, the amino acid sequence of the peptide has been identified as: Gly-Asn-His-Trp-Ala-Val-Gly-His-Leu-Met-NH2. This peptide is found to be identical with the carboxy-terminal subsequence [18-27] of gastrin releasing peptide, and to display a potent contractile activity on rat uterus in the characteristic manner of bombesin. These facts strongly suggest that the peptide may be a neuromediator in the neural communication systems of mammals. We propose the name "neuromedin C" for this peptide, since it is closely related to "neuromedin B", recently identified as a bombesin-like mammalian peptide.
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PMID:Neuromedin C: a bombesin-like peptide identified in porcine spinal cord. 654 86

As a model of pseudopregnancy, the lower esophageal sphincter pressure and plasma gastrin and basal gastric pH levels were determined before and after diuresis in 10 men with tense ascites due to cirrhosis of the liver. Prior to diuresis, when abdominal pressure was increased, sphincter pressure was increased. After diuresis, when ascites was no longer a clinical problem, sphincter pressure was normal. None of the men had heartburn or demonstrable acid reflux either before or after diuresis. In addition, no differences in basal fasting levels of gastrin or gastric pH were noticed before and after diuresis. This study refutes a role for increased abdominal pressure due to an enlarging uterus in the pathogenesis of the heartburn of pregnancy. Moreover, it is consistent with those studies which suggest that increasing progesterone levels seen during pregnancy induce a loss of basal lower esophageal sphincter pressure and thereby allow the occurrence of acid reflux which produces symptomatic heartburn.
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PMID:Evidence refuting a role for increased abdominal pressure in the pathogenesis of the heartburn associated with pregnancy. 724 57

Previous studies have shown that a peptide closely related to gastrin releasing peptide (GRP) is expressed by the pregnant ovine endometrium throughout gestation, however its molecular form and the mode of its secretion have not been defined. We have partially purified the endometrial GRP-like peptide and characterised it chromatographically. In contrast to other tissues, the main molecular form of endometrial GRP is larger (6-8 kDa versus 1-3 kDa), and based on the increased hydrophobicity of its circulating form after reduction, contains at least one disulfide bond. Reduction and treatment with chaotropic agents showed that the protein is not a cleavage product of pro-GRP bound to a binding protein. Tryptic cleavage demonstrated that the C-terminus of the peptide is closely related to GRP18-27 suggesting that bioactivity is likely. The partially purified peptide remained intact after incubation in ovine plasma for 16 h indicating that it is extremely stable and consistent with an hormonal role during pregnancy. Quantification of peptide from monolayer cultures of ovine endometrial cells showed that the GRP-like peptide was secreted constitutively. These data show that a stable, GRP-like peptide, distinct from the known processing products of pre-pro-GRP is constitutively expressed by the gravid ovine endometrium. Since endometrial GRP has an intact bioactive C-terminus and is mitogenic for numerous tissues including the uterus, then it is likely to play an important regulatory role in ovine pregnancy.
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PMID:The pregnant ovine endometrium constitutively expresses and secretes a highly stable bombesin-like peptide, which shares C-terminal sequence but differs structurally from gastrin-releasing peptide. 881 26

Methyleugenol, a food flavor and fragrance agent, was tested for toxicity in male and female F344/N rats and B6C3F1 mice. Groups of 10 males and 10 females per sex per species were administered 0, 10, 30, 100, 300 or 1000 mg methyleugenol/kg body weight in 0.5% aqueous methylcellulose by gavage, 5 days per week for 14 weeks. Additional groups of rats and mice of each sex were dosed similarly and used for hematology and clinical chemistry studies. Groups of 10 male and 10 female rats and mice received the vehicle by gavage on the same dosing schedule and served as vehicle controls. For serum gastrin, gastric pH and cell proliferation studies groups of 10 female rats were given 0, 37, 75 or 150 mg/kg, once daily 5 days per week for 30 or 90 days or 300 or 1000 mg/kg for 30 days; male mice were given 0, 9, 18.5, 37, 75, 150 or 300 mg/kg for 30 or 90 days. For the gastrin, pH and cell proliferation studies, groups of 10 female rats and 10 male mice were given the vehicle for 30 or 90 days and served as controls. Methyleugenol administration to rats induced erythrocyte microcytosis and thrombocytosis in male and female rats. It also caused an increase in serum alanine aminotransferase and sorbitol dehydrogenase activities and bile acid concentration, suggesting hepatocellular injury, cholestasis or altered hepatic function. Additionally, methyleugenol induced hypoproteinemia and hypoalbuminemia, evidenced by decreased total protein and albumin concentrations in both male and female rats, suggesting in inefficiency of dietary protein utilization due to methyleugenol-induced toxic effects on the liver and glandular stomach of rats and mice. The increase in gastrin and gastric pH of rats and mice given methyleugenol suggests that gastrin feedback was impaired and resulted in conditions not conducive to protein digestion. In rats, methyleugenol caused an increase in the incidences of hepatocyte cytologic alteration, cytomegaly, Kupffer cell pigmentation, mixed foci of cellular alteration and bile duct hyperplasia of the liver and atrophy and chronic inflammation of the mucosa of the glandular stomach. In mice, it caused an increase in the incidence of cytologic alteration, necrosis, bile duct hyperplasia and subacute inflammation of the liver and atrophy, degeneration, necrosis, edema, mitotic alteration, and cystic glands of the fundic region of the glandular stomach. The increased incidences of adrenal gland cortical hypertrophy and/or cytoplasmic alteration in the submandibular salivary glands, adrenal glands, testis and uterus of rats were considered secondary to the chemical-related effects observed in the liver and glandular stomach. Based on mortality, body weight gain, clinical chemistry and gross and microscopic evaluation of tissues of rats and mice, the no-observed-effect level (NOEL) of methyleugenol for both species was estimated at 10 mg/kg.
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PMID:14-Week toxicity and cell proliferation of methyleugenol administered by gavage to F344 rats and B6C3F1 mice. 1129 78

Type I and/or type II interferons (IFNs) are important in establishing uterine receptivity to implantation in mammals. Gene expression effected by IFNs may be induced, stimulated or inhibited, but most are IFN-stimulated genes (ISGs). Effects of IFNs range from pregnancy recognition signaling in ruminants by IFN tau (IFNT) to effects on cellular functions of the uterus and uterine vasculature. For most, if not all, actions of IFNs on the uterus, progesterone (P(4)) is permissive to ISG expression, with genes being induced by IFN or induced by P(4) and stimulated by IFN. Uterine receptivity to implantation is P(4)-dependent; however, implantation events are preceded by loss of expression of progesterone (PGR) and estrogen (ESR1) receptors by uterine epithelia. Thus, P4 likely stimulates PGR-positive stromal cells to express one or more progestamedins, e.g., fibroblast growth factors-7 and -10, and/or hepatocyte growth factor, that act via their respective receptors on uterine epithelia and trophectoderm to regulate expression of ISGs. FGF10 appears to be the most important progestamedin in sheep uteri during pregnancy. Sequential effects of P(4) to induce and IFNs to stimulate gene expression suggest that P(4) and IFNs activate complimentary cell signaling pathways to modulate expression of genes for attachment of trophectoderm to uterine lumenal and superficial glandular epithelia (LE/sGE), modify phenotype of uterine stromal cells, silence PGR and ESR1 genes, signal pregnancy recognition, suppress genes for immune recognition, alter membrane permeability to enhance conceptus-maternal exchange of factors, increase endometrial vascularity and activate genes for transport of nutrients into the uterine lumen. In ewes, IFNT abrogrates the uterine luteolytic mechanism and stimulates expression of classical ISGs by GE and stromal cells, whereas LE/sGE express P(4)-induced and IFNT-stimulated genes important for uterine receptivity to implantation and conceptus development. These include wingless-type MMTV (mouse mammary tumor virus) integration site family member 7A (WNT7A) induced by IFNT, as well as galectin, proteases, protease inhibitors, transporters for glucose and amino acids, gastrin releasing polypeptide, insulin-like growth factor binding protein 1 and a hypoxia inducible factor. The specific functions of IFNs and ISGs induced in primates, pigs and other mammals during pregnancy are not known, but likely are important in establishment of pregnancy. Understanding the roles of IFNs and ISGs in uterine receptivity for implantation is necessary to develop strategies to enhance reproductive health and fertility in humans and domestic animals. The magnitude of the LH surge was reduced in cows receiving endotoxin.
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PMID:Interferons and progesterone for establishment and maintenance of pregnancy: interactions among novel cell signaling pathways. 1909 83


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