Linked Life Data

8798442

Source:http://linkedlifedata.com/resource/pubmed/id/8798442

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
37
pubmed:dateCreated
1996-11-7
pubmed:abstractText
Inverse agonists are ligands that are capable of repressing basal receptor activity in the absence of an agonist. We have designed a series of C-1-substituted acetylenic retinoids that exhibit potent antagonism of retinoic acid receptor (RAR)-mediated transactivation. Comparison of these related retinoid antagonists for their ability to repress basal RAR transcriptional activity demonstrates that the identity of the C-1 substituent differentiates these ligands into two groups: RAR inverse agonists and neutral antagonists. We show that treatment of cultured human keratinocytes with a RAR inverse agonist, but not a RAR neutral antagonist, leads to the repression of the serum-induced differentiation marker MRP-8. While RAR-selective agonists also repress expression of MRP-8, cotreatment with a RAR inverse agonist and a RAR agonist results in a mutual repression of their individual inhibitory activities, indicating the distinct modes of action of these two disparate retinoids in modulating MRP-8 expression. Our data indicate that RARs, like beta2-adrenoreceptors, are sensitive to inverse agonists and that this new class of retinoids will provide insight into the molecular mechanisms of RAR function in skin and other responsive tissues.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
22692-6
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Identification and functional separation of retinoic acid receptor neutral antagonists and inverse agonists.
pubmed:affiliation
Department of Biology, Retinoid Research, Allergan Pharmaceuticals, Irvine, California 92715, USA.
pubmed:publicationType
Journal Article