The platelet P2 receptors in inflammation

Cattaneo, Marco

doi:10.5482/hamo-14-09-0044

Cited by 22 publications

(17 citation statements)

References 76 publications

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“…Additional evidence for a role of the platelet P2Y 12 receptor in human asthma was provided by recent clinical observations that P2Y 12 receptor variants were associated with altered lung function in a large familybased asthma cohort and that prasugrel tended to decrease the bronchial hyper-reactivity to mannitol in patients with allergic asthma in a randomized placebo-controlled trial. 35 In sharp contrast, a recent study reported no involvement of P2Y 12 in allergic inflammation in ovalbumin-challenged mice, whereas the platelet P2Y 1 receptor appeared to be pivotal (see below). 44 Obviously, there are conflicting data concerning the part played by the P2Y 12 receptor in asthma, and whether the discrepancies might be related to differences in the mouse models of allergic inflammation or to the use of P2Y 12 receptor antagonists versus P2Y 12 −/− mice will require further investigation.…”

Section: 41mentioning

confidence: 72%

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Purinergic Receptors in Thrombosis and Inflammation

Hechler

Gachet

2015

ATVB

142

101

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Abstract-Under various pathological conditions, including thrombosis and inflammation, extracellular nucleotide levels may increase because of both active release and passive leakage from damaged or dying cells. Once in the extracellular compartment, nucleotides interact with plasma membrane receptors belonging to the P2 purinergic family, which are expressed by virtually all circulating blood cells and in most blood vessels. In this review, we focus on the specific role of the 3 platelet P2 receptors P2Y 1 , P2Y 12 , and P2X 1 in hemostasis and arterial thrombosis. Beyond platelets, these 3 receptors, along with the P2Y 2 , P2Y 6 , and P2X 7 receptors, constitute the main P2 receptors mediating the proinflammatory effects of nucleotides, which play important roles in various functions of circulating blood cells and cells of the vessel wall. Each of these P2 receptor subtypes specifically contributes to chronic or acute vascular inflammation and related diseases, such as atherosclerosis, restenosis, endotoxemia, and sepsis. The potential for therapeutic targeting of these P2 receptor subtypes is also discussed.

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Section: 41mentioning

confidence: 72%

“…6,35,36 In addition, the P2Y 12 receptor expressed on VSMCs has been reported to promote proinflammatory and mitogenic responses through a thrombin-induced pathway in vitro. 37 All these findings point to a potential contribution of this receptor to inflammatory diseases.…”

Section: P2y 12 Receptor In Inflammationmentioning

confidence: 99%

Purinergic Receptors in Thrombosis and Inflammation

Hechler

Gachet

2015

ATVB

142

101

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“…Evidence has also emerged for a role to the platelet P2Y 12 R in the pathogenesis of allergic bronchial asthma [59]. Cysteinyl leukotrienes (LTs) LTC 4 , LTD 4 and LTE 4 are biologically active lipids that play a role in allergic asthma [60].…”

Section: Role Of P2y 12 R In Platelet Responses To Agonists Other Thamentioning

confidence: 99%

P2Y12 receptors: structure and function

Cattaneo

2015

Journal of Thrombosis and Haemostasis

Self Cite

123

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To cite this article: Cattaneo M. P2Y 12 receptors: structure and function. J Thromb Haemost 2015; 13 (Suppl. 1): S10-S6.Summary. The platelet P2Y 12 receptor (P2Y 12 R) for adenosine 5 0 diphosphate (ADP) plays a central role in platelet function, hemostasis, and thrombosis. Patients with inherited P2Y 12 R defects display mild-to-moderate bleeding diatheses. Defects of P2Y 12 R should be suspected when ADP, even at high concentrations (≥ 10 lM), is unable to induce full, irreversible platelet aggregation. P2Y 12 R also plays a role in inflammation: its role in the pathogenesis of allergic asthma has been well characterized. In addition, inhibition or genetic deficiency of P2Y 12 R has antitumor effects. Drugs inhibiting P2Y 12 R are potent antithrombotic drugs. Clopidogrel is the P2Y 12 R antagonist that is most widely used in the clinical setting. Its most important drawback is its inability to inhibit adequately P2Y 12 R-dependent platelet function in about onethird of patients. New drugs, such as prasugrel and ticagrelor, which effectively inhibit P2Y 12 R in the vast majority of patients, have proved to be more efficacious than clopdidogrel in preventing major adverse cardiovascular events.

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“…ATP and P2X3R have a long history of involvement with pain and inflammation [21,22]. In colitis, more internal ATP was produced and expression of P2X3R at the end of colorectal nerves was also increased, thus leading to hypersensitivity of rectocolon [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of estrogen receptor beta on P2X3 receptors during inflammation in rats

Jiang

Sun

et al. 2016

Purinergic Signalling

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Estrogen receptor beta (ERβ) has been shown to play a therapeutic role in inflammatory bowel disease (IBD). However, the mechanism underlying how ERβ exerts therapeutic effects and its relationship with P2X3 receptors (P2X3R) in rats with inflammation is not known. In our study, animal behavior tests, visceromotor reflex recording, and Western blotting were used to determine whether the therapeutic effect of ERβ in rats with inflammation was related with P2X3R. In complete Freund adjuvant (CFA)-induced chronic inflammation in rats, paw withdrawal threshold was significantly decreased which were then reversed by systemic injection of ERβ agonists, DPN or ERB-041. In 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats, weight loss, higher DAI scores, increased visceromotor responses, and inflammatory responses were reversed by application of DPN or ERB-041. The higher expressions of P2X3R in dorsal root ganglia (DRG) of CFA-treated rats and those in rectocolon and DRG of TNBS-treated rats were all decreased by injection of DPN or ERB-041. DPN application also inhibited P2X3R-evoked inward currents in DRG neurons from TNBS rats. Mechanical hyperalgesia and increased P2X3 expression in ovariectomized (OVX) CFA-treated rats were reversed by estrogen replacements. Furthermore, the expressions of extracellular signal-regulated kinase (ERK) in DRG and spinal cord dorsal horn (SCDH) and c-fos in SCDH were significantly decreased after estrogen replacement compared with those of OVX rats. The ERK antagonist U0126 significantly reversed mechanical hyperalgesia in the OVX rats. These results suggest that estrogen may play an important therapeutic role in inflammation through downregulation of P2X3R in peripheral tissues and the nervous system, probably via ERβ, suggesting a novel therapeutic strategy for clinical treatment of inflammation.

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The platelet P2 receptors in inflammation

Cited by 22 publications

References 76 publications

Purinergic Receptors in Thrombosis and Inflammation

Purinergic Receptors in Thrombosis and Inflammation

P2Y12 receptors: structure and function

Inhibitory effect of estrogen receptor beta on P2X3 receptors during inflammation in rats

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