Linked Life Data

18005341

Source:http://linkedlifedata.com/resource/pubmed/id/18005341

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-1-31
pubmed:abstractText
3-methyl-6-chloro-7,8-hydroxy-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959), a selective agonist for the putative phosphatidylinositol (PI)-linked dopamine receptor (DAR), has been shown to possess potent anti-Parkinson disease effects but produces less dyskinesia and motor fluctuation that are frequently observed in Parkinson disease drug therapies. The present study was designed to detect the neuroprotection of SKF83959 and its potential mechanism for the effect in cultured rat cortical cells. The presence of SKF83959 with a dose range of 0.1-30 micromol/L improved H2O2-reduced cell viability in a dose-dependent manner. The anti-apoptotic action of SKF83959 was partially abolished by pre-application of the D1 antagonist SCH23390 (30 micromol/L) and the PI 3-kinase (PI 3-K) inhibitor LY294002 but not by the MEK1/2 inhibitor PD98059 (30 micromol/L). Moreover, SKF83959 treatment significantly inhibited H2O2-activated glycogen synthase kinase-3beta (GSK-3beta) which was associated with the drug's neuroprotective effect, but this inhibition was attenuated by SCH23390 and a selective PI 3-K inhibitor. Moreover, the application of either SKF83959 or a pharmacological inhibitor of GSK-3beta attenuated the inhibition by H2O2 on the expression of inducible NO synthase and production of NO. This indicates that D1-like receptor, presumably PI-linked D1 receptor, -mediated alteration of PI 3-K/Akt/GSK-3beta pathway is involved in the neuroprotection by SKF83959. In addition, SKF83959 also effectively decreased the level of the lipid peroxidation and increased the activity of GSH-peroxidase altered by H2O2. These results suggest that SKF83959 exerts its neuroprotective effect through both receptor-dependent and independent mechanisms: Inhibition of GSK-3beta and consequently increasing the expression of inducible NO synthase via putative PI-linked DAR; and its anti-oxidative activity which is independent of DAR.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1471-4159
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
104
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
946-56
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Neuroprotective effects of atypical D1 receptor agonist SKF83959 are mediated via D1 receptor-dependent inhibition of glycogen synthase kinase-3 beta and a receptor-independent anti-oxidative action.
pubmed:affiliation
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't