Disease relevance of P2RY11

• P2Y11 has previously been shown to be expressed in human acute promyelocytic leukemia (APL) HL-60 and NB4 cell lines, and both cell types elevate cyclic AMP (cAMP) levels upon stimulation with extracellular ATP [1].
• The recently cloned canine P2Y11 receptor (cP2Y11) and its human homolog (hP2Y11) were stably expressed in Chinese hamster ovary cells (CHO-K1) and 1321N1 human astrocytoma cells, and their agonist selectivities and coupling efficiencies to phospholipase C and adenylyl cyclase were assessed [2].
• Increased risk of acute myocardial infarction and elevated levels of C-reactive protein in carriersof the Thr-87 variant of the ATP receptor P2Y11 [3].

High impact information on P2RY11

• ATP gradients inhibit the migratory capacity of specific human dendritic cell types: implications for P2Y11 receptor signaling [4].
• Extracellular NAD+ Is an Agonist of the Human P2Y11 Purinergic Receptor in Human Granulocytes [5].
• The rank order of potency of various analogs (AR-C67085 > adenosine 5'-O-(3-thiotriphosphate) = 2'- and 3'-O-(4-benzoyl-benzoyl) ATP > ATP > 2-methylthio-ATP) was close to that of the recombinant human P2Y11 receptor [6].
• Furthermore, these compounds activated cAMP production in DC, in a xanthine-insensitive way, consistent with the involvement of the P2Y11 receptor, which among P2Y subtypes has the unique feature of being dually coupled to phospholipase C and adenylyl cyclase activation [6].
• Northern blot analysis detected human P2Y11 receptor messenger RNA in spleen and HL-60 cells [7].

Chemical compound and disease context of P2RY11

• A pharmacological characterization of the recombinant human P2Y11 receptor has been conducted following stable expression in two different cell lines: the 1321N1 astrocytoma cells for inositol trisphosphate measurements and the CHO-K1 cells for cyclic AMP assays [8].

Biological context of P2RY11

• All cloned and functionally expressed P2Y-receptors are able to couple to phospholipase C. The P2Y11-receptor mediates in addition a stimulation of adenylate cyclase and the tp2y-receptor an inhibition of this signal transduction pathway [9].
• Clones encoding a new human P2Y receptor, provisionally called P2Y11, have been isolated from human placenta complementary DNA and genomic DNA libraries [7].
• Our pharmacological data support the involvement of P2Y11 and P2Y1 purinergic receptors in the downregulation of these major monocyte recruiters [10].
• Transient transfection of Calu-6/P2Y11 cells with constructs containing 896 bp of human REN 5'-flanking DNA linked to the luciferase reporter gene led to a 5.8+/-0.6-fold increase (mean+/-SEM) in reporter activity in response to ATP (P=0.0015) [11].
• Synthesis and structure-activity relationships of suramin-derived P2Y11 receptor antagonists with nanomolar potency [12].

Anatomical context of P2RY11

• The P2Y1 and surprisingly the P2Y11 receptors were the most abundantly expressed P2Y receptors in the endothelium [13].
• The level of P2Y11 transcripts was strongly increased in these cells after granulocyte differentiation induced by retinoic acid or dimethyl sulfoxide [7].
• It is proposed that P2Y11 is responsible for the ATP-mediated differentiation of these cells lines and that this receptor may play a role in the maturation of granulocytic progenitors in the bone marrow [14].
• Pharmacological characterisation of the P2Y11 receptor in stably transfected haematological cell lines [1].
• However, K562 and U937 cells stably transfected with P2Y11 (K11 and U11 cells, respectively) were responsive to extracellular ATP, with an EC50 of 31 and 21 microM, respectively [1].

Associations of P2RY11 with chemical compounds

• In addition, the results with 2,3-O-(4-benzoyl)-benzoyl-ATP indicate that the P2Y11 receptor may be present on the luminal side [15].
• The human P2Y11-receptor is activated by ATP as naturally occurring agonist and it is blocked by suramin and reactive blue 2 (RB2) [16].
• AR-C67085 (2-propylthio-beta,gamma-difluoromethylene-d-ATP, a P2Y11-selective agonist), adenosine 5'-O-(3-thiotriphosphate), and benzoyl ATP were all full agonists with potencies similar to those of ATP and UTP [17].
• It was insensitive to UTP and antagonist pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid) suggesting the involvement of P2Y11 receptor in the observed neuritogenic effect [18].
• These results are similar to those observed for HL-60 cells and NB4 cells implicating P2Y11 as the receptor responsible for the ATP-induced cAMP elevations in these cells [1].

Other interactions of P2RY11

• No mRNA transcripts for P2Y2 or P2Y4 were detectable in the P2Y11-expressing cells [17].
• Treatment of Calu-6/P2Y11 cells with 1 mmol/L ATP caused a 3-fold increase in renin mRNA and protein over 36 hours [11].
• On the other hand, the inhibitory effect of ATP on TNF-alpha release was completely reversed by 5'-AMPS (a P2Y11 receptor antagonist) as well as by H-89, an inhibitor of cAMP-activated PKA [19].

References