Linked Life Data

20599769

Source:http://linkedlifedata.com/resource/pubmed/id/20599769

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2010-9-6
pubmed:abstractText
The adenosine A(1) receptor is a promising therapeutic target for neurological disorders such as cognition deficits and is involved in cardiovascular preconditioning. Classically adenosine receptor agonists were all derivatives of adenosine, and thought to require a D-ribose moiety. More recently, however, the discovery of non-adenosine agonists for the human adenosine A(1) receptor (hA(1)R) has challenged this dogma (Beukers et al., 2004). In this study we characterize the tritiated form of one of these compounds, [(3)H]LUF5834, as the first non-ribose partial agonist radioligand with nanomolar affinity for the hA(1)R. Due to its partial agonist efficacy, [(3)H]LUF5834 labeled both G protein-coupled and uncoupled receptors with a similar high affinity. Using [(3)H]LUF5834 we performed competition binding experiments to characterize a range of A(1)R ligands varying in efficacy from the full agonist CPA to the inverse agonist DPCPX. Surprisingly, in the control condition both agonists and inverse agonists displayed biphasic isotherms. With the addition of 1mM GTP the high affinity isotherm of agonists or the low affinity isotherm of inverse agonists was lost revealing the mechanism of action of such inverse agonists at the A(1)R. Consequently, [(3)H]LUF5834 represents a novel high affinity radioligand for the A(1)R and may prove a useful tool to provide estimates of inverse agonist efficacy at this receptor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1873-2968
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
80
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1180-9
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Characterization of [3H]LUF5834: A novel non-ribose high-affinity agonist radioligand for the adenosine A1 receptor.
pubmed:affiliation
Division of Medicinal Chemistry, Leiden/Amsterdam Centre for Drug Research, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands. jrlane@chem.leidenuniv.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't