Thrombin-induced platelet endostatin release is blocked by a proteinase activated receptor-4 (PAR4) antagonist

British Journal of Pharmacology
L MaJ L Wallace

Abstract

Endostatin is a potent endogenous inhibitor of angiogenesis that was recently shown to be stored in platelets and released in response to thrombin, but not ADP. In the present study, we have tested the hypothesis that thrombin-induced endostatin release from rat platelets is mediated via proteinase-activated receptor-4 (PAR4). Immunoprecipitation and Western blotting confirmed that endostatin is contained within rat platelets. Aggregation and release of endostatin could be elicited by thrombin (0.5 - 1.0 U ml(-1)) or by specific PAR4 agonist (AYPGKF-NH(2); AY-NH(2); 15 - 50 microM). Significant release of endostatin could be induced by a dose of thrombin below that necessary for induction of aggregation. An adenosine diphosphate (ADP) scavenger, apyrase, inhibited the platelet aggregation induced by thrombin, but not the release of endostatin. In contrast, a selective PAR4 antagonist (trans-cinnamoyl-YPGKF-NH(2); tcY-NH(2)) prevented endostatin release and aggregation induced by thrombin or by AY-NH(2). We conclude that thrombin-induced endostatin release from rat platelets is PAR4-mediated via an ADP-independent mechanism that can occur independently of platelet aggregation.

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Citations

Sep 5, 2002·International Journal of Cancer. Journal International Du Cancer·Nils GlenjenØystein Bruserud
Sep 27, 2005·Digestive Diseases and Sciences·Rafael PeriniLi Ma
Jun 27, 2003·Microvascular Research·Barden ChanVikas P Sukhatme
Apr 18, 2007·The Journal of Experimental Medicine·Rashmi SoodHartmut Weiler
Sep 3, 2013·International Journal of Rheumatic Diseases·Hanan Mohamed FaroukAl Hussein M El Dakrony
Apr 24, 2007·Biochemistry. Biokhimii︠a︡·A V DigtyarS E Severin
Nov 28, 2008·Blood·Giannoula Lakka KlementJudah Folkman
Jan 14, 2005·The Keio Journal of Medicine·Lawrence L HorstmanYeon S Ahn
Dec 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Li MaJohn L Wallace
Nov 24, 2011·Advances in Hematology·P SchneiderM Vasse
Apr 21, 2012·Journal of Comparative Pathology·S CurottoC Bulla
Feb 1, 2011·Pharmacology & Therapeutics·Mark N AdamsJohn D Hooper
Jun 2, 2009·The Journal of Surgical Research·Giorgio PietramaggioriDennis P Orgill
Dec 4, 2008·Journal of Proteomics·Sander R PiersmaConnie R Jiménez
Nov 8, 2008·The American Journal of Pathology·Giorgio PietramaggioriDennis P Orgill
Aug 14, 2012·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Myriam DefontisDavid Ledieu
May 27, 2014·Frontiers in Endocrinology·Peishen ZhaoNigel W Bunnett
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Jul 16, 2019·Hepatology Communications·Alexandre BalaphasLeo H Bühler
Mar 21, 2021·The FEBS Journal·Arundhasa Chandrabalan, Rithwik Ramachandran

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