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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1992-7-27
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
131
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
374-80
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Characterization of nuclear angiotensin-II-binding sites in rat liver and comparison with plasma membrane receptors.
pubmed:affiliation
Molecular and Cellular Vascular Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't