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  • 1
    Digitale Medien
    Digitale Medien
    Differences in the determinants of eplerenone, spironolactone and aldosterone binding to the mineralocorticoid receptor (2004)
    Oxford, UK : Blackwell Science Pty
    Clinical and experimental pharmacology and physiology 31 (2004), S. 0 
    Details
    ISSN: 1440-1681
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: 1. The importance of mineralocorticoid receptor (MR) antagonists in the treatment of cardiovascular disease has been emphasised by two recent clinical trials, one using spironolactone and the other using a new selective MR antagonist, namely eplerenone.2. Eplerenone has a very low affinity for the glucocorticoid receptor (GR). Determinants of binding specificity of eplerenone to the MR were investigated using chimeras created between the ligand-binding domains (LBD) of the MR and the GR. These chimeras had been used previously to investigate aldosterone and spironolactone binding specificity to the MR.3. Eplerenone competed strongly for [3H]-dexamethasone binding to a MR/GR chimera containing amino acids 804–874 of the MR and weakly to a chimera containing amino acids 672–803 of the MR. Within the 804–874 region, eplerenone competed for [3H]-dexamethasone binding to a chimera containing amino acids 820–844 of the MR, although the calculated affinity was approximately 10-fold lower than for binding to the full-length MR LBD. Similar results were obtained using another MR antagonist, namely spironolactone. Modelling of eplerenone binding to the MR LBD, based on the GR LBD crystal structure, suggests that amino acids 820–844 affect the overall shape of the ligand-binding pocket and that eplerenone acts as an MR antagonist because it fails to stabilize the active conformation of the receptor.4. In contrast with results with the MR antagonists eplerenone and spironolactone, amino acids 820–844 are sufficient in themselves to confer high-affinity aldosterone binding to the MR, suggesting that the binding determinants of the two antagonists are similar to each other but differ from those of aldosterone.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1440-1681.2004.04079.x
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  • 2
    Digitale Medien
    Digitale Medien
    TRANSCRIPTIONAL CONTROL BY CORTICOSTEROIDS OF CHIF GENE EXPRESSION IN THE RAT DISTAL COLON (1999)
    Melbourne, Australia : Blackwell Science Pty
    Clinical and experimental pharmacology and physiology 26 (1999), S. 0 
    Details
    ISSN: 1440-1681
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: 1. Previous studies have shown that levels of CHIF mRNA are increased in the distal colon of the rat in response to corticosteroids. We have recently reported that this response occurs within 2 h of a single dose of either dexamethasone or aldosterone and that the response is mediated via both the mineralocorticoid and glucocorticoid receptors.2. In the present study we sought to further define the nature of the various transcripts detected by a CHIF coding region cRNA probe in northern blot analysis of corticosteroid- stimulated colonic RNA. The identification of an intronic sequence was used to synthesize an intron-specific cDNA probe to characterize the transcripts.3. The presence of an intronic sequence in the originally published sequence was confirmed using coupled reverse transcriptase–polymerase chain reactions with primers spanning and within the intronic sequence. The intronic cDNA probe hybridized to the higher molecular weight transcripts detected by the cRNA probe. These transcripts are induced in response to both corticosteroids.4. Taken together with our observations that the increase in CHIF mRNA levels in the distal colon in response to corticosteroids is not blocked by prior cycloheximide treatment, the increase in the levels of the primary transcript and partially spliced forms argues that this is a primary transcriptional response. This is the first clear demonstration of an aldosterone-induced gene in vivo in a mammalian system.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1046/j.1440-1681.1999.03065.x
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  • 3
    facet.materialart.
    Unbekannt
    Ottocento (1970)
    London, etc. : Periodicals Archive Online (PAO)
    The Year's work in modern language studies. 32 (1970) 432 
    Details
    ISSN: 0084-4152
    Thema: Allgemeine und vergleichende Sprach- und Literaturwissenschaft. Indogermanistik. Außereuropäische Sprachen und Literaturen
    Beschreibung / Inhaltsverzeichnis: ITALIAN STUDIES
    Notizen: ROMANCE LANGUAGES
    URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pao:&rft_dat=xri:pao:article:0015-1970-032-00-000035
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  • 4
    facet.materialart.
    Unbekannt
    Ottocento (1971)
    London, etc. : Periodicals Archive Online (PAO)
    The Year's work in modern language studies. 33 (1971) 442 
    Details
    ISSN: 0084-4152
    Thema: Allgemeine und vergleichende Sprach- und Literaturwissenschaft. Indogermanistik. Außereuropäische Sprachen und Literaturen
    Beschreibung / Inhaltsverzeichnis: ITALIAN STUDIES
    Notizen: ROMANCE LANGUAGES
    URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pao:&rft_dat=xri:pao:article:0015-1971-033-00-000032
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  • 5
    Digitale Medien
    Digitale Medien
    Acute differential regulation by corticosteroids of epithelial sodium channel subunit and Nedd4 mRNA levels in the distal colon (2000)
    Springer
    Pflügers Archiv 441 (2000), S. 94-101 
    Details
    ISSN: 1432-2013
    Schlagwort(e): Aldosterone Dexamethasone ENaC Glucocorticoid Mineralocorticoid
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract. The molecular mechanisms by which corticosteroids affect fluid and electrolyte balance have yet to be fully elucidated. The apical amiloride-sensitive electrogenic epithelial sodium channel (ENaC) has been shown to have a central role in corticosteroid-mediated sodium transport in the distal colon. The acute response of the α-, β- and γ ENaC subunit genes to a single parenteral dose of aldosterone or dexamethasone was examined in the rat distal colon in vivo. The response of the Nedd4 gene, whose product is involved in channel turnover, was also examined. Whilst the α ENaC and Nedd4 genes showed no significant response to either steroid, both the β- and γENaC mRNA levels were increased acutely by both aldosterone and dexamethasone. The γENaC mRNA appears to have a very short half-life. Use of the highly selective glucocorticoid receptor agonist RU28362 confirmed that the response was mediated by both the mineralocorticoid and glucocorticoid receptors.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004240000366
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  • 6
    Digitale Medien
    Digitale Medien
    POU-domain gene expression in the gastrointestinal tract (1995)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 58 (1995), S. 260-267 
    Details
    ISSN: 0730-2312
    Schlagwort(e): adaptation ; small bowel ; gut development ; homeogenes ; Oct-1 ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: The process of self-renewal which occurs in the gastrointestinal epithelium is greatly amplified and accelerated during the intestinal adaptation which occurs in the residual ileum after massive small bowel resection (MSBR). As with growth and development, these processes must involve the coordinated regulation of many genes. Several families of nuclear proteins are known to be involved in the control of gene expression during development including the POU-domain genes; their expression has not been characterized in the gastrointestinal tract during normal cellular renewal or adaptation, and POU-domain encoding cDNAs were cloned from ileal RNA. Three known genes were cloned: Oct-1, Brn-1 and Tst-1 but no novel members of this gene family were identified. The encoded sequence for rat Oct-1 differs from that previously reported. Oct-1 is relatively ubiquitously expressed with increased expression during both development and adaptation. Minimal expression of Tst-1 was observed. Brn-1 exhibits limited expression in the adult gastrointestinal tract. but may play a role in the fetal gastrointestinal tract.
    Zusätzliches Material: 3 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/jcb.240580214
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