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PAR1 contribution in acute electrophysiological properties of oral anticoagulants in rabbit pulmonary vein sleeve preparations.Whether oral anti-coagulants, vitamin K antagonists (VKAs) and non-vitamin K oral anticoagulant (NOACs) frequently prescribed to atrial fibrillation (AF) patients, do themselves have a pro- or anti-arrhythmic effect have never been addressed. Transmembrane action potentials were recorded in an acute rabbit model of superfused pulmonary veins (PVs) sleeves preparations using standard microelectrode technique. Fluindione 10 μmol/L (n = 6) increased the AP (action potential) duration (APD), induced a significantly Vdepression (from 95±14 to 53±5 V/s, P < 0.05) and 2:1 blocks during rapid atrial pacing thus evoking class I antiarrhythmic properties, and prevented spontaneous trigger APs. Apixaban 10 μmol/L (n = 6) increased the APD, significantly prolonged the effective refractory period (from 56.3±4.2 to 72.0±8.6 ms, P<0.05) and prevented triggered APs occurrence. Fluindione and apixaban effects were suppressed with the addition of the protease-activated receptors 1 (PAR 1) agonist SFLLR-NH. Warfarin 10 μmol/L (n = 6) significantly abbreviated the early refractory period (from 56.3±4.2 to 45.0±2.2 ms, P<0.05) and increased triggered APs occurrence that were successfully prevented by nifedipine but not by the addition of the protease-activated receptors 1 agonist SFLLR-NH. In this acute rabbit PVs model, VKAs and NOACs, at physiological concentrations, exhibited very different pharmacological properties that influence PVs electrophysiology, implying PAR1, with fluindione and apixaban which exhibited more antiarrhythmic properties whereas warfarin exhibited more proarrhythmic properties. This article is protected by copyright. All rights reserved.
2249 related Products with: PAR1 contribution in acute electrophysiological properties of oral anticoagulants in rabbit pulmonary vein sleeve preparations.Interleukin-34 IL34 (N-t Interleukin-34 IL34 anti Integrin â3 (Phospho Tyr Integrin â3 (Phospho Tyr Interferon-a Receptor Typ Goat Anti-Human F2R PAR1, Rabbit Anti-Inf A Neurami Rabbit Anti-Influenza A H Rabbit Anti-Influenza A N Rabbit Anti-Influenza-A H Rabbit Anti-Influenza-A H Rabbit Anti-Influenza-A H
#27426918 // Save this To Up
Protease-activated receptor-1 negatively regulates proliferation of neural stem/progenitor cells derived from the hippocampal dentate gyrus of the adult mouse.Thrombin-activated protease-activated receptor (PAR)-1 regulates the proliferation of neural cells following brain injury. To elucidate the involvement of PAR-1 in the neurogenesis that occurs in the adult hippocampus, we examined whether PAR-1 regulated the proliferation of neural stem/progenitor cells (NPCs) derived from the murine hippocampal dentate gyrus. NPC cultures expressed PAR-1 protein and mRNA encoding all subtypes of PAR. Direct exposure of the cells to thrombin dramatically attenuated the cell proliferation without causing cell damage. This thrombin-induced attenuation was almost completely abolished by the PAR antagonist RWJ 56110, as well as by dabigatran and 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), which are selective and non-selective thrombin inhibitors, respectively. Expectedly, the PAR-1 agonist peptide (AP) SFLLR-NH2 also attenuated the cell proliferation. The cell proliferation was not affected by the PAR-1 negative control peptide RLLFT-NH2, which is an inactive peptide for PAR-1. Independently, we determined the effect of in vivo treatment with AEBSF or AP on hippocampal neurogenesis in the adult mouse. The administration of AEBSF, but not that of AP, significantly increased the number of newly-generated cells in the hippocampal subgranular zone. These data suggest that PAR-1 negatively regulated adult neurogenesis in the hippocampus by inhibiting the proliferative activity of the NPCs.
1271 related Products with: Protease-activated receptor-1 negatively regulates proliferation of neural stem/progenitor cells derived from the hippocampal dentate gyrus of the adult mouse.anti Transferrin receptor Normal mouse multiple org Mouse Anti-Human CD34 Tar Rat monoclonal anti mouse Rat monoclonal anti mouse Mouse Anti-Bacteroides th 129 Mouse Embryonic Stem Pfu DNA Polymerase protei Mouse Anti-Human Estrogen Mouse Anti-Human Thyroid Mouse Anti-Human Thyroid Macrophage Colony Stimula
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Expression of proteinase-activated receptor (PAR)-2 in monocytes from allergic patients and potential molecular mechanism.Serine proteases play an important role in inflammation via PARs. However, little is known of expression levels of PARs on monocytes of allergic patients, and influence of serine proteases and PARs on TNF-α secretion from monocytes. Using quantitative real-time PCR (qPCR) and flowcytometry techniques, we observed that the expression level of PAR-2 in monocytes of patients with allergic rhinitis and asthma was increased by 42.9 and 38.2 %. It was found that trypsin, thrombin, and tryptase induced up to 200, 320, and 310 % increase in TNF-α release from monocytes at 16 h, respectively. PAR-1 agonist peptide, SFLLR-NH, and PAR-2 agonist peptide tc-LIGRLO-NHprovoked up to 210 and 240 % increase in release of TNF-α. Since SCH 79797, a PAR-1 antagonist, and PD98059, an inhibitor of ERK inhibited thrombin- and SFLLR-NH-induced TNF-α release, the action of thrombin is most likely through a PAR-1- and ERK-mediated signaling mechanism. Similarly, because FSLLRN-NH, an inhibitor of PAR-2 diminished tryptase- and tc-LIGRLO-NH-induced TNF-α release, the action of tryptase appears PAR-2 dependent. Moreover, in vivo study showed that both recombinant cockroach major allergens Per a 1 and Per a 7 provoked upregulation of PAR-2 and PAR-1 expression on CD14+ cells in OVA-sensitized mouse peritoneum. In conclusion, increased expression of PAR-2 in monocytes of AR and asthma implicates that PAR-2 likely play a role in allergy. PAR-2- and PAR-1-mediated TNF-α release from monocytes suggests that these unique protease receptors are involved in the pathogenesis of inflammation.
2590 related Products with: Expression of proteinase-activated receptor (PAR)-2 in monocytes from allergic patients and potential molecular mechanism.Polyclonal Antibody Prote Mouse Anti-Human Interleu Rabbit Anti-Human Androge IGF-1R Signaling Phospho- Insulin Receptor Phospho- Human soluble interleukin Goat Anti-Human Serotonin Rabbit Anti-Human Vasoact Polyclonal Antibody Recep Androgen Receptor Ab-1 An Androgen Receptor Ab 1 Androgen Receptor
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Protease activated receptor 1 (PAR1) enhances Src-mediated tyrosine phosphorylation of NMDA receptor in intracerebral hemorrhage (ICH).It has been demonstrated that Src could modulate NMDA receptor, and PAR1 could also affect NMDAR signaling. However, whether PAR1 could regulate NMDAR through Src under ICH has not yet been investigated. In this study, we demonstrated the role of Src-PSD95-GluN2A signaling cascades in rat ICH model and in vitro thrombin challenged model. Using the PAR1 agonist SFLLR, antagonist RLLFS and Src inhibitor PP2, electrophysiological analysis showed that PAR1 regulated NMDA-induced whole-cell currents (INMDA) though Src in primary cultured neurons. Both in vivo and in vitro results showed the elevated phosphorylation of tyrosine in Src and GluN2A and enhanced interaction of the Src-PSD95-GluN2A under model conditions. Treatment with the PAR1 antagonist RLLFS, AS-PSD95 (Antisense oligonucleotide against PSD95) and Src inhibitor PP2 inhibited the interaction among Src-PSD95-GluN2A, and p-Src, p-GluN2A. Co-application of SFLLR and AS-PSD95, PP2, or MK801 (NMDAR inhibitor) abolished the effect of SF. In conclusion, our results demonstrated that activated thrombin receptor PAR1 induced Src activation, enhanced the interaction among Src-PSD95-GluN2A signaling modules, and up-regulated GluN2A phosphorylation after ICH injury. Elucidation of such signaling cascades would possibly provide novel targets for ICH treatment.
2478 related Products with: Protease activated receptor 1 (PAR1) enhances Src-mediated tyrosine phosphorylation of NMDA receptor in intracerebral hemorrhage (ICH).IGF-1R Signaling Phospho- T-Cell Receptor Signaling Goat Anti-Rat NMDA recept interleukin 17 receptor C interferon-alpha receptor anti Transferrin receptor Insulin Receptor Phospho- Nuclear Membrane Receptor Rabbit Anti-Insulin Recep Rabbit Anti-Insulin Recep Rabbit Anti-Insulin Recep Rabbit Anti-Insulin Recep
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Antiplatelet and antithrombotic effect of F 16618, a new thrombin proteinase-activated receptor-1 (PAR1) antagonist.New antithrombotic agents with the potential to prevent atherothrombotic complications are being developed to target receptors on platelets and other cells involved in plaque growth. The aim of this study was to investigate the antiplatelet effects of F 16618, a new non-peptidic PAR1 (thrombin receptor) antagonist.
2898 related Products with: Antiplatelet and antithrombotic effect of F 16618, a new thrombin proteinase-activated receptor-1 (PAR1) antagonist.Rabbit Anti-PAR-1 Thrombi Rabbit Anti-PAR-1 Thrombi Rabbit Anti-PAR-1 Thrombi Rabbit Anti-PAR-1 Thrombi Rabbit Anti-PAR-1 Thrombi Polyclonal Antibody Prote Goat Anti-Human F2R PAR1, Rabbit Anti-Human Androge RANK Ligand Soluble, Huma FGF Receptor 1 (Ab 154) A Cytokine receptor-like fa G protein-coupled recepto
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Induction of apoptosis by thrombin in the cultured neurons of dorsal motor nucleus of the vagus.A previous study demonstrated the presence of protease-activated receptor (PAR) 1 and 2 in the dorsal motor nucleus of vagus (DMV). The aim of this study is to characterize the effect of thrombin on the apoptosis of DMV neurons.
2340 related Products with: Induction of apoptosis by thrombin in the cultured neurons of dorsal motor nucleus of the vagus.Thermal Shaker with cooli FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu Ofloxacin CAS Number [824 Multiple organ tumor tiss MultiGene Gradient therm BACTERIOLOGY BACTEROIDES TCP-1 theta antibody Sour
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Transient receptor potential canonical 3 (TRPC3) mediates thrombin-induced astrocyte activation and upregulates its own expression in cortical astrocytes.Reactive astrogliosis, defined by abnormal morphology and excessive cell proliferation, is a characteristic response of astrocytes to CNS injuries, including intracerebral hemorrhage. Thrombin, a major blood-derived serine protease, leaks into the brain parenchyma upon blood-brain barrier disruption and can induce brain injury and astrogliosis. Transient receptor potential canonical (TRPC) channels, Ca(2+)-permeable, nonselective cation channels, are expressed in astrocytes and involved in Ca(2+) influx after receptor stimulation; however, their pathophysiological functions in reactive astrocytes remain unknown. We investigated the pathophysiological roles of TRPC in thrombin-activated cortical astrocytes. Application of thrombin (1 U/ml, 20 h) upregulated TRPC3 protein, which was associated with increased Ca(2+) influx after thapsigargin treatment. Pharmacological manipulations revealed that the TRPC3 upregulation was mediated by protease-activated receptor 1 (PAR-1), extracellular signal-regulated protein kinase, c-Jun NH(2)-terminal kinase, and nuclear factor-κB signaling and required de novo protein synthesis. The Ca(2+) signaling blockers BAPTA-AM, cyclopiazonic acid, and 2-aminoethoxydiphenyl borate and a selective TRPC3 inhibitor, pyrazole-3, attenuated TRPC3 upregulation, suggesting that Ca(2+) signaling through TRPC3 contributes to its increased expression. Thrombin-induced morphological changes at 3 h upregulated S100B, a marker of reactive astrocytes, at 20 h and increased astrocytic proliferation by 72 h, all of which were inhibited by Ca(2+)-signaling blockers and specific knockdown of TRPC3 using small interfering RNA. Intracortical injection of SFLLR-NH(2), a PAR-1 agonist peptide, induced proliferation of astrocytes, most of which were TRPC3 immunopositive. These results suggest that thrombin dynamically upregulates TRPC3 and that TRPC3 contributes to the pathological activation of astrocytes in part through a feedforward upregulation of its own expression.
2030 related Products with: Transient receptor potential canonical 3 (TRPC3) mediates thrombin-induced astrocyte activation and upregulates its own expression in cortical astrocytes.DNA (cytosine 5) methyltr AZD-3514 Mechanisms: Andr Rabbit Anti-Insulin Recep Rabbit Anti-Insulin Recep Rabbit Anti-Insulin Recep Rabbit Anti-PAR-1 Thrombi Goat Anti-Human, Rat Sero Anti-AICDA(Activation-ind Anti AICDA(Activation ind Interleukin-34 IL34 (N-t Interleukin-34 IL34 anti Sterile filtered mouse s
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Protease-activated receptor 1 antagonists prevent platelet aggregation and adhesion without affecting thrombin time.The aim of this study was to investigate the in vitro antithrombotic effects of two PAR1 antagonists, ER121958 and SCH203099 on both SFLLR-induced platelet adhesion and aggregation and on the thrombin time in human and guinea-pig platelets. ER121958 inhibited SFLLR-induced guinea-pig and human platelet adhesion with the IC(50) values of 1.73nM and 2.91nM, respectively and SFLLR-induced guinea-pig and human platelet aggregation with the IC(50) values of 2.74nM and 11.9nM, respectively. Similarly, SCH203099 exhibited a non competitive profile of inhibition on both SFLLR-induced guinea-pig and human platelet adhesion with the IC(50) values of 93nM and 127nM, respectively or SFLLR-induced guinea-pig and human platelet aggregation with the IC(50) values of 1.74microM and 2.36microM, respectively. These two antagonists failed to prolong the thrombin time. Altogether, these results highlighted the potent anti-platelets properties of both ER121958 and SCH203099 in an in vitro model of aggregation as well as in a static model of adhesion without any effect on the last step of coagulation cascade. Moreover, this work emphasized that guinea-pig is a suitable animal model to study the role of PAR1 antagonists since the magnitude of the effects of ER121958 and SCH203099 on both SFLLR-induced platelet adhesion and aggregation were similar in both species.
2337 related Products with: Protease-activated receptor 1 antagonists prevent platelet aggregation and adhesion without affecting thrombin time.Rabbit Anti-Human Androge anti Transferrin receptor Rabbit Anti-PAR-1 Thrombi Rabbit Anti-PAR-1 Thrombi Rabbit Anti-PAR-1 Thrombi Rabbit Anti-PAR-1 Thrombi Rabbit Anti-PAR-1 Thrombi Rabbit Anti-PAR-1 Thrombi Rabbit Anti-PAR-1 Thrombi Rabbit Anti-PAR-1 Thrombi Rabbit Anti-PAR-1 Thrombi Rabbit Anti-PAR-1 Thrombi
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Antithrombotic activity of F 16618, a new PAR1 antagonist evaluated in extracorporeal arterio-venous shunt in the rat.The purpose of the present work was the evaluation of the antithrombotic activity of a new PAR1 antagonist, F 16618 in arterio-venous shunt in the rat. Arterial thrombosis was induced by insertion of a silk thread (thrombogenic substrate) into an extracorporeal shunt. F 16618 was administered either by intravenous route (0.63-2.5mg/kg) or by oral route (20-80mg/kg). Oral activity of F 16618 was compared to that of aspirin (20-80mg/kg) and clopidogrel (0.63-10mg/kg). Finally, F 16618 was associated to aspirin and/or clopidogrel to test for possible antithrombotic activity and its effects on bleeding time. SFLLR-induced human platelet aggregation was evaluated in the presence of F 16618, demonstrating the anti-aggregant activity of this compound. F 16618 (1.25mg/kg) significantly delayed the time leading to occlusion by 52+/-17%, without affecting bleeding time and in absence of hemodynamic effects. F 16618 given orally dose-dependently increased the time to occlusion. The maximal effect was observed at 40mg/kg (984+/-95s versus 644+/-17s in vehicle group). Aspirin and clopidogrel also dose-dependently lengthened time to occlusion, but this effect was associated with an increase of bleeding time. F 16618 (20mg/kg) orally associated with either aspirin (40mg/kg) or with clopidogrel (1.25mg/kg) potentiated the antithrombotic effects of both compounds without further increasing of bleeding time. In conclusion, F 16618 exerted a potent antithrombotic activity by intravenous and oral routes, without affecting bleeding time. Furthermore, the antithrombotic activity was potentiated when combined with aspirin or clopidogrel.
1933 related Products with: Antithrombotic activity of F 16618, a new PAR1 antagonist evaluated in extracorporeal arterio-venous shunt in the rat.Goat Anti-Human F2R PAR1, Cell Meter™ Fluorimetri Cell Meter™ Fluorimetri Rabbit Anti-intestinal FA Rabbit Anti-APIP Apaf1 In Rabbit Anti-APIP Apaf1 In Rat intestinal fatty acid Rat Anti-Mouse Interleuki ELISA kit CLGI,Collagenas EnzyChrom™ Kinase Assay Goat Anti-Human, Rat FOXP FDA Standard Frozen Tissu
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Kallikrein-related peptidase 4: a new activator of the aberrantly expressed protease-activated receptor 1 in colon cancer cells.Certain serine proteases are considered to be signaling molecules that act through protease-activated receptors (PARs). Our recent studies have implicated PAR1 and PAR4 (thrombin receptors) and PAR2 (trypsin receptor) in human colon cancer growth. Here we analyzed the expression of KLK4, a member of the kallikrein-related peptidase (KLK) family of serine proteases and explored whether this member can activate PAR1 and PAR2 in human colon cancer cells. Immunohistochemistry showed KLK4 expression in human colon adenocarcinomas and its absence in normal epithelia. KLK4 (1 micromol/L) initiated loss of PAR1 and PAR2 from the HT29 cell surface as well as increased intracellular calcium transients in HT29 cells. This KLK4-induced Ca2+ flux was abrogated after an initial challenge of the cells with TRAP (SFLLR-NH2; 100 micromol/L), which is known to desensitize PAR1 and PAR2. Interestingly, PAR1 blocking antibody, which inhibits cleavage and activation by thrombin, dramatically reduced KLK4-induced Ca2+ influx, but blocking cleavage of PAR2 failed to attenuate the KLK4-induced Ca2+ flux. Consistently, desensitization with AP1 (TFFLR-NH2), targeting PAR1, attenuated most of the Ca2+ flux induced by KLK4. KLK4 also induced a rapid and significant ERK1/2 phosphorylation in HT29 cells. Our results demonstrate, for the first time, that KLK4 is aberrantly expressed in colon cancer and capable of inducing PAR1 signaling in cancer cells. These data suggest that KLK4 signaling via PAR1 may represent a novel pathway in colon tumorigenesis.
2348 related Products with: Kallikrein-related peptidase 4: a new activator of the aberrantly expressed protease-activated receptor 1 in colon cancer cells.RANK Ligand Soluble, Huma anti Transferrin receptor Colon cancer and normal t Colon cancer and normal t Colon cancer and matched Colon cancer tissue array Colon cancer tissue array Colon cancer tissue array Colon cancer high density Colon disease spectrum (c Colon cancer survey tissu High density colon cancer
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