Involvement of thromboxane A2 and tyrosine kinase in the synergistic interaction of platelet activating factor and calcium ionophore A23187 in human platelet aggregation

Rasheed, Huma; Saeed, Sheikh A.

doi:10.1038/emm.2004.30

Cited by 14 publications

(11 citation statements)

References 18 publications

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“…26,27 Consistent with this, EKA/B was found to synergise with a number of other agonists. Platelets stimulated with 1.25 μM EKA/B, 0.005 U/mL thrombin, 0.5 μg/mL collagen, 10 μM adrenaline, or 10 μM 5-HT displayed little or no evidence of aggregation.…”

Section: Resultssupporting

confidence: 60%

Peripheral tachykinins and the neurokinin receptor NK1 are required for platelet thrombus formation

Jones

Tucker

Sage

et al. 2008

Blood

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Platelets play an important role in hemostasis, with inappropriate platelet activation being a major contributor to debilitating and often fatal thrombosis by causing myocardial infarction and stroke. Although current antithrombotic treatment is generally well tolerated and effective, many patients still experience cardiovascular problems, which may reflect the existence of alternative underlying regulatory mechanisms in platelets to those targeted by existing drugs. In this study, we define a role for peripherally distributed members of the tachykinin family of peptides, namely substance P and the newly discovered endokinins A and B that are present in platelets, in the activation of platelet function and thrombus formation. We have reported previously that the preferred pharmacologically characterized receptor for these peptides, the NK1 receptor, is present on platelets. Inhibition or deficiency of the NK1 receptor, or SP agonist activity, resulted in substantially reduced thrombus formation in vitro under arterial flow conditions, increased bleeding time in mice, and a decrease in experimentally induced thromboembolism. Inhibition of the NK1 receptor may therefore provide benefit in patients vulnerable to thrombosis and may offer an alternative therapeutic target.

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Section: Resultssupporting

confidence: 60%

Peripheral tachykinins and the neurokinin receptor NK1 are required for platelet thrombus formation

Jones

Tucker

Sage

et al. 2008

Blood

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“…There are several lines of evidence that PAR‐mediated Ca 2+ mobilization is coupled to PI‐PLC ( Mule et al ., 2002 ; Oshiro et al ., 2002 ). Nevertheless, the results in Figure 4 revealed that the PAR2‐mediated responses were unaffected by PI‐PLC inhibitors, such as U73122 ( K i =4–10 μ M ) ( Connor et al ., 2001 ; Saeed et al ., 2003 ; Rasheed & Saeed, 2004 ) or ET‐18‐OCH 3 ( K i =2–18 μ M ) ( Powis et al ., 1992 ; Daniel et al ., 1995 ; Seebeck et al ., 1998 ), and an InsP 3 inhibitor, Xest C ( K i =0.3–0.4 μ M ) ( Gafni et al ., 1997 ). However, recent studies have shed light on PC‐PLC as an alternative pathway for production of DAG ( Snetkov et al ., 2001 ).…”

Section: Discussionmentioning

confidence: 99%

Ion transport regulated by protease‐activated receptor 2 in human airway Calu‐3 epithelia

Sato

Ito

Kondo

et al. 2005

British J Pharmacology

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1 We examined the mechanisms underlying anion secretion mediated by protease-activated receptor 2 (PAR2) and its role in the regulation of ion transport, using polarized human airway Calu-3 cells. 2 PAR2 stimulation by trypsin and a PAR2-activating peptide (PAR2AP), especially from the basolateral aspect, caused transient Cl À secretion due to cytosolic Ca 2 þ mobilization. 3 Antagonists of PI-PLC (U73122, ET-18-OCH 3 ) and inositol 1,4,5-triphosphate (xestospongin C (Xest C)) were without effect on the PAR2AP-mediated Cl À secretion, whereas it was attenuated by D609 (a PC-PLC inhibitor) and phorbol 12-myristate 13 acetate (PMA, a PKC activator). 4 Even 30 min after removal of PAR2AP after a 10-min-exposure, cells were still poorly responsive to PAR2 stimulation, but the reduced responsiveness was upregulated by a PKC inhibitor, GF109203X (GFX). 5 Pretreatment with PAR2AP did not affect responses to anion secretagogues, such as isoproterenol, forskolin, thapsigargin, 1-ethyl-2-benzimdazolinone, and adenosine, but ATP-induced responses were significantly reduced. Nystatin permeabilization studies revealed that the presence of PAR2AP prevented ATP-induced increments in basolateral membrane K þ conductance without affecting apical membrane Cl À conductance. 6 ATP-elicited Ca 2 þ mobilization, which was sensitive to D609 and PMA, was inhibited by the pretreatment with PAR2AP, and this inhibition was blunted by the presence of GFX. 7 Collectively, stimulation of PAR2 generates a brief response of Cl À secretion through PC-PLCmediated pathway, followed by not only auto-desensitization of PAR2 itself but also crossdesensitization of a PC-PLC-coupled purinoceptor. The two types of desensitization seem likely to have PKC-mediated downregulation of PC-PLC in common.

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“…Similar inhibitory effects of LT and MAPK inhibitors were also observed in the platelet aggregation experiments, which showed that LT, PD98059, and SB203580 could significantly inhibit the platelet aggregation induced by AA treatment (figure 2B), and quantitative results showed that the inhibitory effects of reagent treatments are consistent with the results of the fibrinogen adhesion experiments (figure 2A and 2C). Previous studies have demonstrated that thrombin-, collagen-, and PAF-induced platelet activations are less sensitive to MAPK inhibitors [22,42]. If LT inhibits platelet activities primarily through MAPK pathways, the inhibition should be less effective when platelets are stimulated with these agonists.…”

Section: Whole-blood Clotting Inhibition By Anthrax Lt Treatmentmentioning

confidence: 99%

Antiplatelet Activities of Anthrax Lethal Toxin Are Associated with Suppressed p42/44 and p38 Mitogen‐Activated Protein Kinase Pathways in the Platelets

et al. 2005

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Anthrax lethal toxin (LT) is the major virulence factor produced by Bacillus anthracis, but the mechanism by which it induces high mortality remains unclear. We found that LT treatment could induce severe hemorrhage in mice and significantly suppress human whole-blood clotting and platelet aggregation in vitro. In addition, LT could inhibit agonist-induced platelet surface P-selectin expression, resulting in the inhibition of platelet-endothelial cell engagements. Data from Western blot analysis indicated that LT treatment resulted in the suppression of p42/44 and p38 mitogen-activated protein kinase pathways in platelets. Combined treatments with LT and antiplatelet agents such as aspirin and the RGD-containing disintegrin rhodostomin significantly increased mortality in mice. Our data suggest that platelets are a pathogenic target for anthrax LT.

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Involvement of thromboxane A2 and tyrosine kinase in the synergistic interaction of platelet activating factor and calcium ionophore A23187 in human platelet aggregation

Cited by 14 publications

References 18 publications

Peripheral tachykinins and the neurokinin receptor NK1 are required for platelet thrombus formation

Peripheral tachykinins and the neurokinin receptor NK1 are required for platelet thrombus formation

Ion transport regulated by protease‐activated receptor 2 in human airway Calu‐3 epithelia

Antiplatelet Activities of Anthrax Lethal Toxin Are Associated with Suppressed p42/44 and p38 Mitogen‐Activated Protein Kinase Pathways in the Platelets

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