Linked Life Data

15861463

Source:http://linkedlifedata.com/resource/pubmed/id/15861463

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-5-4
pubmed:abstractText
Until recently, there was a lack of selective radioligands for the subtypes of metabotropic glutamate (mGlu) receptors. [(3)H]LY354740 ((+)-2-aminobicyclo[3,1,0]hexane-2,6-dicarboxylic acid), a selective agonist for group II receptors (mGlu2 and -3, which are negatively coupled to cAMP production), has now been used to map their brain distribution and abundance by in vitro binding and quantitative radioautography. The selective cation dependence of its binding allowed the discrimination between mGlu2 and mGlu3 receptor labeling. Thus, in the presence of Ca(2+) and Mg(2+) ions, the agonist bound selectively to mGlu2 receptors as evidenced by: 1) the correlative distribution and abundance of binding sites (highest in the lacunosum moleculare of the hippocampus and lowest in white matter) with mGlu2 receptor mRNA and protein revealed by in situ hybridization histochemistry and immunohistochemistry, respectively; 2) its selective pharmacology; and 3) the distribution of LY354740-stimulated [(35)S]GTPgammaS binding (25-97% above basal, according to the brain region), revealing G protein-coupled receptor coupling to G(i) proteins. Nonspecific binding (in the presence of 10 muM DCG-IV, a group II-selective, mGlu2-preferring, receptor agonist) was <10% of total. In adjacent sections, the distribution of binding sites for [(3)H]DCG-IV was very similar. This extensive study paves the way for investigations of the regional expression and regulation of mGlu2 receptors in human CNS diseases, such as Alzheimer's disease, which may reveal their functional roles and identify potential therapeutic drug targets. Indeed, it has recently been demonstrated (Higgins et al. [2004] Neuropharmacology 46:907-917) that pharmacological manipulation of mGlu2 receptors influences cognitive performance in the rodent.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9967
pubmed:author
pubmed:copyrightInfo
(c) 2005 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
487
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15-27
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Distribution and abundance of metabotropic glutamate receptor subtype 2 in rat brain revealed by [3H]LY354740 binding in vitro and quantitative radioautography: correlation with the sites of synthesis, expression, and agonist stimulation of [35S]GTPgammas binding.
pubmed:affiliation
Pharma Research Basel, Neuroscience Discovery, F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland. richards@balcab.ch
pubmed:publicationType
Journal Article, Comparative Study, Validation Studies