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 @entity2036 , such as @entity6883 (ATP) and @entity20548 (UTP). A previous report suggested that UTP may be a biased agonist at the @entity1 @entity23462 receptor, as it increased cytosolic [ @entity141 ], but did not induce accumulation of @entity7256 , 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 @entity23462 receptor in greater detail. Intracellular @entity141 was monitored in 1321N1 cells stably expressing @entity1 @entity23462 receptors using the @entity141 -sensitive fluorescent indicator, @entity20048 . ATP evoked a rapid, concentration-dependent rise in intracellular @entity141 , 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 @entity141 in 1321N1 cells stably expressing the @entity1 P2Y2 receptor, with no difference in the maximum response. Thus, the lack of response to UTP at @entity23462 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 @entity1 @entity23462 receptor, nor does UTP act as an antagonist.

UTP is not a biased agonist at @entity1 XXXX receptors.

@entity1 :: ('9606', 'Species') :: ['human'] @entity23462 :: ('5032', 'Gene') :: ['P2Y11', 'hP2Y11'] @entity2036 :: ('MESH:D009711', 'Chemical') :: ['nucleotides'] @entity6883 :: ('CHEBI:15422', 'Chemical') :: ['adenosine 5   -triphosphate'] @entity20048 :: ('MESH:C409648', 'Chemical') :: ['fluo-4'] @entity20548 :: ('CHEBI:15713', 'Chemical') :: ['uridine 5   -triphosphate'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca2+'] @entity7256 :: ('MESH:D007295', 'Chemical') :: ['inositol phosphates']
@entity23462 :: (5032,Gene) :: ['P2Y(11)']
