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Characterization of [3H]LUF5834: A novel non-ribose high-affinity agonist radioligand for the adenosine A1 receptor

Lane, J Robert; Klaasse, Elisabeth; Lin, Judy; van Bruchem, John; Beukers, Margot W; Ijzerman, Adriaan P


Associate Professor

Elisabeth Klaasse

Judy Lin

John van Bruchem

Margot W Beukers

Adriaan P Ijzerman


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.


Lane, J. R., Klaasse, E., Lin, J., van Bruchem, J., Beukers, M. W., & Ijzerman, A. P. (2010). Characterization of [3H]LUF5834: A novel non-ribose high-affinity agonist radioligand for the adenosine A1 receptor. Biochemical Pharmacology, 80(8), 1180-1189.

Journal Article Type Article
Acceptance Date Jun 22, 2010
Online Publication Date Jun 30, 2010
Publication Date Oct 15, 2010
Deposit Date Apr 22, 2020
Journal Biochemical Pharmacology
Print ISSN 0006-2952
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 80
Issue 8
Pages 1180-1189
Public URL
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