Linked Life Data

7738355

Source:http://linkedlifedata.com/resource/pubmed/id/7738355

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1995-6-2
pubmed:abstractText
Among retinoic acid receptors (RARs) alpha, beta, and gamma, the messenger RNA level of RAR-gamma is the most readily detectable by Northern blotting in human and mouse skin. This observation suggests that RAR-gamma may play a critical role in the modulation of the therapeutic benefits and side effects of retinoids in skin. To test this hypothesis, 11 RAR-gamma selective retinoids were synthesized based on three related structures. Each compound was found to prefer RAR-gamma when assessed by retinoid-induced transcriptional activity (RAR-gamma > RAR-beta > RAR-alpha). The apparent Kd for binding to recombinant receptor protein was found to follow a similar trend. To correlate this receptor selectivity with in vivo activity, the compounds were tested topically in the Rhino mouse utriculi reduction and rabbit irritation models, two assays widely used to screen retinoids for efficacy and side effects, respectively. The results indicated that for these compounds, both efficacy in the utriculi reduction assay and irritation potential in rabbits correlated positively with the RAR-gamma transactivation activity, with r2 of 0.9 and 0.8, respectively. These data suggest that RAR-gamma is an important regulator of retinoic acid efficacy in skin and further, that the irritation associated with the use of retinoids is most likely a receptor-mediated process.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-202X
pubmed:author
pubmed:issnType
Print
pubmed:volume
104
pubmed:owner
NLM
pubmed:authorsComplete
N
pubmed:pagination
779-83
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Retinoic acid receptor gamma mediates topical retinoid efficacy and irritation in animal models.
pubmed:affiliation
Bristol-Myers Squibb Pharmaceutical Research Institute, Buffalo, New York 14213, USA.
pubmed:publicationType
Journal Article