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UTP is not a biased agonist at human P2Y11 receptors.

Morrow, Gael B.; Nicholas, Robert A.; Kennedy, Charles


Robert A. Nicholas

Charles Kennedy


Biased agonism describes a multistate model of G protein-coupled receptor activation in which each ligand induces a unique structural conformation of the receptor, such that the receptor couples differentially to G proteins and other intracellular proteins. P2Y receptors are G protein-coupled receptors that are activated by endogenous nucleotides, such as adenosine 5′-triphosphate (ATP) and uridine 5′-triphosphate (UTP). A previous report suggested that UTP may be a biased agonist at the human P2Y11 receptor, as it increased cytosolic [Ca2+], but did not induce accumulation of inositol phosphates, whereas ATP did both. The mechanism of action of UTP was unclear, so the aim of this study was to characterise the interaction of UTP with the P2Y11 receptor in greater detail. Intracellular Ca2+ was monitored in 1321N1 cells stably expressing human P2Y11 receptors using the Ca2+-sensitive fluorescent indicator, fluo-4. ATP evoked a rapid, concentration-dependent rise in intracellular Ca2+, but surprisingly, even high concentrations of UTP were ineffective. In contrast, UTP was slightly, but significantly more potent than ATP in evoking a rise in intracellular Ca2+ in 1321N1 cells stably expressing the human P2Y2 receptor, with no difference in the maximum response. Thus, the lack of response to UTP at hP2Y11 receptors was not due to a problem with the UTP solution. Furthermore, coapplying a high concentration of UTP with ATP did not inhibit the response to ATP. Thus, contrary to a previous report, we find no evidence for an agonist action of UTP at the human P2Y11 receptor, nor does UTP act as an antagonist.


MORROW, G.B., NICHOLAS, R.A. and KENNEDY, C. 2014. UTP is not a biased agonist at human P2Y11 receptors. Purinergic signalling [online], 10(4), pages 581-585. Available from:

Journal Article Type Article
Acceptance Date Jun 30, 2014
Online Publication Date Jul 12, 2014
Publication Date Dec 31, 2014
Deposit Date Aug 7, 2023
Publicly Available Date Aug 15, 2023
Journal Purinergic signalling
Print ISSN 1573-9538
Electronic ISSN 1573-9546
Publisher Springer
Peer Reviewed Peer Reviewed
Volume 10
Issue 4
Pages 581-585
Keywords Biased agonism; P2Y11 receptor; Inositol phosphates; Intracellular Ca2+
Public URL


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