Thrombin Receptors

Bahou, Wadie F.

doi:10.1016/b978-012369367-9/50771-0

Cited by 10 publications

(13 citation statements)

References 237 publications

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“…To develop an approach to examining platelet activation versus apoptosis, we treated human platelets with three agents, a pro-apoptotic BH3-only mimetic, the anti-cancer drug ABT-737 (Oltersdorf et al, 2005;Mason et al, 2007;Zhang et al, 2007;Dasgupta et al, 2010;Mutlu et al, 2012), the potent platelet agonist thrombin (Coughlin, 2005;Lundblad & White, 2005;Leytin et al, 2006aLeytin et al, , 2007Bahou, 2007;Lopez et al, 2008) and calcium ionophore A23187 (Leytin et al, 2004(Leytin et al, , 2006a(Leytin et al, , 2009Rand et al, 2004;Mutlu et al, 2012), known inducers of apoptosis and/or activation in nucleated cells and platelets. We concurrently determined an apoptosis marker, depolarization of mitochondrial inner transmembrane potential (DΨm) (Kroemer & Reed, 2000;Leytin et al, 2004Leytin et al, , 2006aLeytin et al, , 2007Leytin et al, , 2009Rand et al, 2004;Gyulkhandanyan et al, 2012), and a marker of platelet activation, exposure of P-selectin (CD62) on the platelet surface (Stenberg et al, 1985;Michelson et al, 1991;Leytin et al, 2000aLeytin et al, , 2007.…”

Section: Discussionmentioning

confidence: 99%

Selective triggering of platelet apoptosis, platelet activation or both

et al. 2013

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SummaryAnucleate platelets perform two fundamental processes, activation and apoptosis. We elaborated an approach for selective and concurrent stimulation of platelet apoptosis and/or activation, processes important in haemostasis and platelet clearance. Human platelets were treated with BH3 mimetic ABT-737, thrombin, calcium ionophore A23187 and matched diluents. Apoptosis was determined as mitochondrial inner membrane potential (DΨm) depolarization and activation as P-selectin exposure. At optimal treatment conditions (90-180 min, 37°C), ABT-737 predominantly induced apoptosis, when 77-81% platelets undergo only DΨm depolarization. The ABT-737 impact on DΨm depolarization is strongly time-and temperature-dependent, and much higher at 37°C than at room temperature. In contrast, when platelets were treated with thrombin for 15-90 min at either temperature, activation-only was predominantly (79-85%) induced, whereas A23187 triggers both apoptosis and activation (73-81%) when platelets were treated for 15-60 min at 37°C or 15-90 min at room temperature. These data demonstrate that, depending on the triggering stimulus, platelets predominantly undergo DΨm depolarization-only, P-selectin exposure-only, or both responses, indicating that platelet apoptosis and activation are different phenomena driven by different mechanisms. The described model provides a basis for studying differential pharmacological manipulation of platelet apoptosis and activation and their role in haemostasis, thrombosis and platelet clearance.

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Section: Discussionmentioning

confidence: 99%

Selective triggering of platelet apoptosis, platelet activation or both

et al. 2013

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“…Thrombin binds to protease-activated receptors (PAR-1) and initiates platelet activation through the phospholipase C pathway. When activated, platelets secrete their granule contents and release growth factors (20,21). Findings in this study could be explained by the highly stimulating effect of thrombin on platelet secretion, which may hinder the antiaggregant effects of NSAIDs and ASA.…”

Section: Discussionmentioning

confidence: 77%

Meloxicam and diclofenac do not change VEGF and PDGF-ABserum levels of platelet-rich plasma

et al. 2017

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Background/aim: Platelet-rich plasma (PRP) application has gained widespread interest for musculoskeletal injuries. Nonsteroidal antiinflammatory drugs are frequently used in sports medicine before and/or after PRP application. Our study seeks to determine whether serum levels of platelet-derived growth factor-AB (PDGF-AB) and vascular endothelial growth factor (VEGF) levels of PRP would be affected by nonsteroidal antiinflammatory drugs.Materials and methods: Two different final concentrations of diclofenac (0.5 µg mL -1 and 2.5 µg mL -1 ), meloxicam (0.8 µg mL -1 and 2.0 µg mL -1 ), and acetylsalicylic acid (final concentration 450 µm) were obtained in separate tubes with PRPs prepared from 20 healthy male volunteers. Medicine-free PRP was the control group. Growth factors were measured using ELISA.Results: PDGF-AB and VEGF serum levels did not change with diclofenac, meloxicam, or acetylsalicylic acid addition. PDGF-AB and VEGF serum levels correlated with each other. Conclusion:Diclofenac, meloxicam, and acetylsalicylic acid did not affect PDGF-AB and VEGF serum levels.

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“…On platelets, it carries out the activating potential by inducing proteolytic events and furthermore by binding to the GPIb-V–IX complex ( 1 , 20 – 22 ). Established thrombin substrates include PAR receptors, coagulation factors V, VIII, and XIII, and fibrinogen ( 23 ).…”

Section: Coagulation and Related Proteasesmentioning

confidence: 99%

“…The proteolysis liberates a new N-terminus, which autocatalytically activates the receptor molecule ( 26 , 27 ). By ensuing signaling via G-proteins (in particular Gqα) ( 24 , 28 ), thrombin induces a wide range of platelet responses, including shape change, Ca 2+ fluxes, integrin activation, and secretion ( 23 ).…”

Section: Coagulation and Related Proteasesmentioning

confidence: 99%

Platelet Membrane Receptor Proteolysis: Implications for Platelet Function

Heemskerk

Baaten

2021

Front. Cardiovasc. Med.

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The activities of adhesion and signaling receptors in platelets are controlled by several mechanisms. An important way of regulation is provided by proteolytic cleavage of several of these receptors, leading to either a gain or a loss of platelet function. The proteases involved are of different origins and types: (i) present as precursor in plasma, (ii) secreted into the plasma by activated platelets or other blood cells, or (iii) intracellularly activated and cleaving cytosolic receptor domains. We provide a comprehensive overview of the proteases acting on the platelet membrane. We describe how these are activated, which are their target proteins, and how their proteolytic activity modulates platelet functions. The review focuses on coagulation-related proteases, plasmin, matrix metalloproteinases, ADAM(TS) isoforms, cathepsins, caspases, and calpains. We also describe how the proteolytic activities are determined by different platelet populations in a thrombus and conversely how proteolysis contributes to the formation of such populations.

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Thrombin Receptors

Cited by 10 publications

References 237 publications

Selective triggering of platelet apoptosis, platelet activation or both

Selective triggering of platelet apoptosis, platelet activation or both

Meloxicam and diclofenac do not change VEGF and PDGF-ABserum levels of platelet-rich plasma

Platelet Membrane Receptor Proteolysis: Implications for Platelet Function

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