Participation of peripheral P2Y1, P2Y6 and P2Y11 receptors in formalin-induced inflammatory pain in rats

Barragán-Iglesias, Paulino; Mendoza-Garcés, Luis; Pineda-Farías, Jorge Baruch; Solano-Olivares, Verónica; Rodrı́guez-Silverio, Juan; Flores‐Murrieta, Francisco J.; Granados‐Soto, Vinicio; Rocha-González, Héctor Isaac

doi:10.1016/j.pbb.2014.11.001

Cited by 44 publications

(44 citation statements)

References 78 publications

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“…Other antibodies have also been used to examine the existence of the murine P2Y 11 . The P2Y 11 antibody #AB9590 targeting the human P2Y 11 C-terminus detects a large, 75-kDa band on western blot, which is believed to be P2Y 11 on the basis of the results of experiments using rat tissue [41,42], and it has been claimed that another antibody with an unknown epitope confirms P2Y 11 receptor expression in rat neutrophils with a 40-kDa signal [43].…”

Section: P2y 11 Antibodies Lack Specificitymentioning

confidence: 99%

“…It is also worth noting that NF157, NF340, and NF546 have all been used to study the murine BP2Y 11 -like receptort hat shows many of the same properties as seen in humans [14,[41][42][43][82][83][84]. Assuming that no P2Y 11 receptor exists in murines, these compounds must have other mechanisms by which they interfere with cell signalling.…”

Section: Selective P2y 11 Activation and Inhibitionmentioning

confidence: 99%

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A critical look at the function of the P2Y11 receptor

Dreisig

Kornum

2016

Purinergic Signalling

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The P2Y 11 receptor is a member of the purinergic receptor family. It has been overlooked, somewhat due to the lack of a P2ry11 gene orthologue in the murine genome, which prevents the generation of knockout mice, which have been so helpful for defining the roles of other P2Y receptors. Furthermore, some of the studies reported to date have methodological shortcomings, making it difficult to determine the function of P2Y 11 with certainty. In this review, we discuss the lack of a murine BP2Y 11 -like receptor^and highlight the limitations of the currently available methods used to investigate the P2Y 11 receptor. These methods include protein recognition with antibodies that show very little specificity, gene expression studies that completely overlook the existence of a fusion transcript between the adjacent PPAN gene and P2RY11, and agonists/antagonists reported to be specific for the P2Y 11 receptor but which have not been tested for activity on numerous other adenosine 5′-triphosphate (ATP)-binding receptors. We suggest a set of criteria for evaluating whether a dataset describes effects mediated by the P2Y 11 receptor. Following these criteria, we conclude that the current evidence suggests a role for P2Y 11 in immune activation with cell typespecific effects.

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Section: P2y 11 Antibodies Lack Specificitymentioning

confidence: 99%

Section: Selective P2y 11 Activation and Inhibitionmentioning

confidence: 99%

A critical look at the function of the P2Y11 receptor

Dreisig

Kornum

2016

Purinergic Signalling

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“…Recently though a study in rats by Barragán-Iglesias et al (2015) using FIIP has suggested the involvement and upregulation of peripheral P2Y6 receptors in the development of chronic inflammatory pain; in the same study P2Y11 mRNA was located in rat DRG for the first time, and this was analogously upregulated. Activation of either P2Y6 or P2Y11 receptors before injection of formalin led to increased pain responses as quantified by flinching behaviour, and these were correspondingly reduced by the presence of antagonists prior to formalin injection.…”

Section: P2 Receptors and Painmentioning

confidence: 83%

“…Inhibition or knockout of P2Y1 inhibits the inducement of peripheral inflammatory sensitisation by complete Freund's adjuvant (CFA) (Mallin and Moliver, 2010), and additionally in formalin induced inflammatory pain (FIIP) P2Y1 receptors are similarly pro-nociceptive (Barragán-Iglesias et al, 2015). P2Y2 and/or P2Y4 receptor activation with UTP raises the pain threshold in the hot plate test (Andó et al, 2010), and P2Y2 receptors appear to also be involved with TRPV1 and peripheral sensitisation (Moriyama et al¸ 2003); chronic inflammatory pain has been further reported to upregulate P2Y2 receptor expression (Zhu et al, 2015).…”

Section: P2 Receptors and Painmentioning

confidence: 99%

Biochemical and molecular characterisation of the proposed P2Y1-P2Y12 receptor heterodimer in tsA201 cells

Davis¹

2018

Preprint

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The P2Y receptor family represents a wide-ranging set of G-protein-coupled receptors that respond to purinergic ligands, and are involved in many physiological processes. From signalling assays in tsA201 cells, the Kennedy lab has previously proposed the formation of a constitutive heterodimer between co-expressed human P2Y1 and P2Y12 receptors; this could represent a target for the control of pain sensing neurones. Therefore, it was aimed in this project to characterise if the receptors physically interacted using co-immunoprecipitation, and also to investigate the endogenous expression of other potentially interacting hP2Y receptors in the tsA201 cell line. In this study, tsA201 cells were determined to express mRNA for hP2Y1, 2, 4, 6, 12, 14 receptors using reverse transcriptase PCR and confirmatory Sanger sequencing. Furthermore, the cells demonstrated Ca2+ responses to all of the natural hP2Y receptor agonists tested, the order of potency being ADP > ATP > UTP > UDP. When co-expressing hP2Y1 and hP2Y12 receptors oppositely tagged with a HA or fluorescent protein (FP), immunoprecipitating for the HA tag and blotting for the FP showed a visible high molecular weight protein complex of ~130 to >250 KDa for either combination of receptors. This implied that the FP tagged receptor had co-immunoprecipitated with the other HA tagged receptor as this protein was also visible when blotting for the HA tag, signifying the presence of both tagged receptors in the complex. These results were overall suggestive of functional hP2Y1, 2, 12 receptor expression in the tsA201 cell line, and possibly also hP2Y4, 6, 14 receptors. The high molecular weight protein complex detected could represent a constitutive hP2Y1-hP2Y12 receptor heterodimer as proposed. Whilst it was not possible to specifically either confirm or refute the physical formation of the heterodimer with the data acquired, it was potentially supportive, and furthermore suggested other future paths of investigation.

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“…Other studies have investigated the role of P2Y 1 in neuroinflammation. For example, in a study of neuroinflammation induced by cerebral stroke, it was found that P2Y 1 -null mice exhibited significantly less altered cognitive decline [11]. In another study, peripheral pretreatment with a selective P2Y 1 antagonist resulted in improved nociception in a model of formalininduced inflammatory pain [12].…”

Section: Introductionmentioning

confidence: 99%

Lung injury during LPS-induced inflammation occurs independently of the receptor P2Y1

Liverani

2016

Purinergic Signalling

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Disruption of the lung endothelial and epithelial barriers during acute inflammation leads to excessive neutrophil migration. It is likely that activated platelets promote pulmonary recruitment of neutrophils during inflammation, and previous studies have found that anti-platelet therapy and depletion of circulating platelets have lung-protective effects in different models of inflammation. Because ADP signaling is important for platelet activation, I investigated the role of the ADP-receptor P2Y 1 , a G protein-coupled receptor expressed on the surface of circulating platelets, during lipopolysaccharide (LPS)-induced inflammation and lung injury in P2Y 1 -null and wild-type mice. Systemic inflammation was induced by a single intraperitoneal dose of LPS (3 mg/kg), and the mice were analyzed 24 h posttreatment. The data show that the LPS-induced inflammation levels were comparable in the P2Y 1 -null and wild-type mice. Specifically, splenomegaly, counts of circulating platelets and white blood cells (lymphocytes and neutrophils), and assessments of lung injury (tissue architecture and cell infiltration) were similar in the P2Y 1 -null and wild-type mice. Based on my results, I conclude that lung injury during LPS-induced inflammation in mice is independent of P2Y 1 signaling. I propose that if a blockade of purinergic signaling in platelets is a potential lung-protective strategy in the treatment of acute inflammation, then it is more likely to be a result of the disruption of the signaling pathway mediated by P2Y 12 , another G protein-coupled receptor that mediates platelet responses to ADP.

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Participation of peripheral P2Y1, P2Y6 and P2Y11 receptors in formalin-induced inflammatory pain in rats

Cited by 44 publications

References 78 publications

A critical look at the function of the P2Y11 receptor

A critical look at the function of the P2Y11 receptor

Biochemical and molecular characterisation of the proposed P2Y1-P2Y12 receptor heterodimer in tsA201 cells

Lung injury during LPS-induced inflammation occurs independently of the receptor P2Y1

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