P2Y4, P2Y6 and P2Y11 receptors: From the early days of cloning to their function

Communi, Didier; Horckmans, Michael; Boeynaems, Jean‐Marie

doi:10.1016/j.bcp.2020.114347

Cited by 9 publications

(5 citation statements)

References 66 publications

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“…However, compound 1 is known to affect the levels of adenylyl cyclase and cyclic adenosine monophosphate (cAMP) in immunocompetent cells [37]. This may indicate the putative effect of compound 1 on cell receptors associated with G-protein and adenylyl cyclase activity, such as adrenergic [38] or P2Y receptors [39]. In turn, cAMP as a secondary messenger can play a variety of biological roles [40], including the role of a regulator of the in ammatory process [41], cell proliferation processes [42], and activation of hepatic stellate cells [43].…”

Section: Discussionmentioning

confidence: 99%

Influence of Xymedon and its conjugate with L-ascorbic acid on collagen remodeling in the liver fibrosis rat model

Belyaev,

Vyshtakalyuk,

Parfenov

et al. 2024

Preprint

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Fibrosis of the liver is a chronic inflammatory process with activation of hepatic stellate cells and abnormal accumulation of proteins in the extracellular matrix. However, it is known that pyrimidine derivatives have a beneficial effect on the condition of various organs with the ongoing process of fibrosis. Therefore, the aim of this work was to investigate the effect of the drug Xymedon (1,2-dihydro-4,6-dimethyl-1-N-(2-hydroxyethyl)pyrimidine-2-one, (compound 1) and its conjugate with L-ascorbic acid (compound 2) on collagen remodeling in rat liver tissue. For this purpose, female Wistar rats were used to model fibrosis by oral administration of carbon tetrachloride (CCl4) and ethanol for 8 weeks. Then the rats were treated with the studied compounds for 2 or 4 weeks. Histological analysis by hematoxylin-eosin and Van Gizon’s staining of liver slices, biochemical analysis of blood serum and Western blot analysis of COX-2 level in rat liver homogenates were performed. It has been shown that in the control group without treatment, after 2 weeks of withdrawal of CCl4 + ethanol, collagen remodeling occurs to the certain chronic level. At the same time, compound 2 reduces the level of collagen fibers by 41% compared to the control group, while native compound 1 has no such effect. Also, in all groups studied, there was the decrease in the inflammatory marker COX-2 both after 2 weeks of CCl4 + ethanol withdrawal and after treatment with studied compounds 1 and 2. Thus, compound 2 (conjugate of Xymedon with L-ascorbic acid) has the greater antifibrotic effect on the rat liver fibrosis model compared to the native molecule of compound 1 (Xymedon). At the same time, this effect is not associated with the level of COX-2.

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Section: Discussionmentioning

confidence: 99%

Influence of Xymedon and its conjugate with L-ascorbic acid on collagen remodeling in the liver fibrosis rat model

Belyaev,

Vyshtakalyuk,

Parfenov

et al. 2024

Preprint

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“…A variety of P2Y receptors have been detected in human bone tissue, for example the expression level of P2Y6 is very high [29] and this receptor, a member of P2Y family, is highly selective for nucleotides containing uridine, such as UDP. P2Y6 receptors are expressed in bone, brain, kidney, heart, and many other tissues, but are particularly important for bone development and repair [30,31]. P2Y6 can activate phospholipase C (PLC) by binding to ligands in osteoblasts, which subsequently leads to an increase of intracellular free Ca 2+ and the activation of protein kinase C (PKC), which regulates cell proliferation and differentiation, while in osteoclasts, the activation of P2Y6 receptor prevents TNF α-induced apoptosis [31][32][33].…”

Section: Discussionmentioning

confidence: 99%

Titanium dioxide nanotubes increase purinergic receptor P2Y6 expression and activate its downstream PKCα-ERK1/2 pathway in bone marrow mesenchymal stem cells under osteogenic induction

Wang

Liu

et al. 2023

Acta Biomaterialia

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“…Like P2Y 1 and P2Y 2 receptors, the P2Y 4 receptor couples mainly to G q/11 proteins. However, the P2Y 4 receptor response could partially be inhibited by pertussis toxin, suggesting that the P2Y 4 receptor also couples to G i proteins [ 67 ]. P2Y 4 receptors are expressed in heart, lung, and placenta.…”

Section: P2y 4 Receptormentioning

confidence: 99%

“…The G q -coupled P2Y 6 receptor is preferentially activated by UDP [ 11 , 67 ]. UDP-mediated activation of P2Y 6 receptor promotes the recruitment of inflammatory cells to sites of inflammation or infection by inducing the production of various chemokines including CCL2 (monocyte chemotactic protein 1, MCP-1), CXCL8 (IL-8) and CCL20 (macrophage inflammatory protein-3α, MIP-3α) [ 70 , 71 , 72 , 73 , 74 ].…”

Section: P2y 6 Receptormentioning

confidence: 99%

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Control of Macrophage Inflammation by P2Y Purinergic Receptors

Klaver

Thurnher

2021

Cells

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Macrophages comprise a phenotypically and functionally diverse group of hematopoietic cells. Versatile macrophage subsets engage to ensure maintenance of tissue integrity. To perform tissue stress surveillance, macrophages express many different stress-sensing receptors, including purinergic P2X and P2Y receptors that respond to extracellular nucleotides and their sugar derivatives. Activation of G protein-coupled P2Y receptors can be both pro- and anti-inflammatory. Current examples include the observation that P2Y14 receptor promotes STAT1-mediated inflammation in pro-inflammatory M1 macrophages as well as the demonstration that P2Y11 receptor suppresses the secretion of tumor necrosis factor (TNF)-α and concomitantly promotes the release of soluble TNF receptors from anti-inflammatory M2 macrophages. Here, we review macrophage regulation by P2Y purinergic receptors, both in physiological and disease-associated inflammation. Therapeutic targeting of anti-inflammatory P2Y receptor signaling is desirable to attenuate excessive inflammation in infectious diseases such as COVID-19. Conversely, anti-inflammatory P2Y receptor signaling must be suppressed during cancer therapy to preserve its efficacy.

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P2Y4, P2Y6 and P2Y11 receptors: From the early days of cloning to their function

Cited by 9 publications

References 66 publications

Influence of Xymedon and its conjugate with L-ascorbic acid on collagen remodeling in the liver fibrosis rat model

Influence of Xymedon and its conjugate with L-ascorbic acid on collagen remodeling in the liver fibrosis rat model

Titanium dioxide nanotubes increase purinergic receptor P2Y6 expression and activate its downstream PKCα-ERK1/2 pathway in bone marrow mesenchymal stem cells under osteogenic induction

Control of Macrophage Inflammation by P2Y Purinergic Receptors

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