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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1992-7-27
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pubmed:abstractText |
Although the action of angiotensin-II (Ang-II) is believed to be mediated by a transmembrane signal transduction mechanism, accumulating evidence suggests that Ang-II may also have a direct nuclear action. We have characterized the nuclear Ang-II-binding site in purified nuclei preparation from rat liver and compared it to plasma membrane Ang-II receptors. [125I]Ang-II binding to isolated nuclei reached equilibration in 30 min at 25 C, slower than binding to plasma membrane, which reached equilibration within 10 min. Scatchard analysis of [125I]Ang-II binding to isolated nuclei revealed a single class of binding sites (Kd = 1.4 nM; binding capacity = 10 fmol/mg protein or 460 sites/nucleus). In the nuclear preparation, Ang-II and its fragments competed for binding a potency order of Ang-III = Ang-II greater than Ang-II-(1-7) greater than Ang-II-(1-6) greater than Ang-II-(1-5). Losartan potassium (DuP 753), a selective blocker of the Ang-II receptor subtype I, fully inhibits nuclear Ang-II binding with affinity similar to that in plasma membrane. The pH optimum for [125I]Ang-II binding to nuclei was 7.0, while binding to plasma membrane was optimal at pH 8.0. Low concentrations (0.05-0.1 mM) of dithiothreitol increased [125I]Ang-II binding to nuclei, but not to plasma membrane. In the absence of detergent, Ang-II-binding sites appear to consist of soluble protein releasable from nuclei by freezing and thawing, hence distinct in physicochemical properties from the membrane-bound receptor. Size-exclusion HPLC estimated the mol wt of the soluble Ang-II-binding sites to be 66 kilodaltons. These nuclear Ang-II-binding sites have some similarities to but also show notable physicochemical differences from plasma membrane Ang-II receptors, and they may play a role in mediating the intracellular action of Ang-II.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0013-7227
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
131
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
374-80
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:1612017-Angiotensin II,
pubmed-meshheading:1612017-Animals,
pubmed-meshheading:1612017-Cell Fractionation,
pubmed-meshheading:1612017-Cell Membrane,
pubmed-meshheading:1612017-Cell Nucleus,
pubmed-meshheading:1612017-Dithiothreitol,
pubmed-meshheading:1612017-Hydrogen-Ion Concentration,
pubmed-meshheading:1612017-Kinetics,
pubmed-meshheading:1612017-Liver,
pubmed-meshheading:1612017-Male,
pubmed-meshheading:1612017-Molecular Weight,
pubmed-meshheading:1612017-Peptide Fragments,
pubmed-meshheading:1612017-Rats,
pubmed-meshheading:1612017-Rats, Inbred Strains,
pubmed-meshheading:1612017-Receptors, Angiotensin,
pubmed-meshheading:1612017-Solubility
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pubmed:year |
1992
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pubmed:articleTitle |
Characterization of nuclear angiotensin-II-binding sites in rat liver and comparison with plasma membrane receptors.
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pubmed:affiliation |
Molecular and Cellular Vascular Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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