Linked Life Data

2843743

Source:http://linkedlifedata.com/resource/pubmed/id/2843743

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1988-10-26
pubmed:abstractText
Canrenone is the major metabolic product of the synthetic steroids spironolactone and K+-canrenoate, used in antihypertensive therapy. Canrenone can competitively displace [3H]ouabain from Na,K-ATPase [Na+- and K+-activated, Mg2+-dependent adenosine triphosphatase (E.C.3.6.1.3)] and partially inhibit enzymatic activity. These features have led to a hypothesis that competition between canrenone and endogenous digitalis-like materials, suggested to be involved in etiology of essential hypertension, could underly the antihypertensive effect of canrenone. Surprisingly, three derivatives of canrenone (6 beta,7 alpha-,6 beta,7 beta-, and 6 alpha,7 alpha-dihydroxy-6,7-dihydrocanrenone) reportedly occur in normal human and rat urine. This paper characterizes the interactions with partially purified renal Na,K-ATPase of canrenone, the three 6,7-dihydroxylated derivatives, and one epoxide intermediate, synthesized from K+-canrenoate. Canrenone and all the 6,7-substituted derivatives partially inhibited Na,K-ATPase activity (39-45%), with approximately the same apparent affinity, 100-200 microM. Canrenone displaced [3H]ouabain in an apparently competitive fashion (Ki = 100-300 microM) but none of the tested derivatives significantly displaced ouabain even at very high concentrations. The ability to differentiate the ATPase inhibition and [3H]ouabain displacement by modification of the 6,7-double bond indicates that inhibition of ATPase activity does not occur from within the ouabain binding site. We suggest that neither canrenone nor the 6,7-derivatives bind to the ouabain site, but rather interact with it 'allosterically.' Our findings do not support the proposed mechanisms for the antihypertensive action of canrenone.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
245-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Do canrenone and 6,7-dihydroxylated derivatives compete with ouabain at the same site on Na,K-ATPase?
pubmed:affiliation
Department of Biochemistry, Weizmann Institute of Science, Rehovot, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't