Physiology, pharmacology, and therapeutic potential of protease-activated receptors in vascular disease

Pharmacology & Therapeutics
Hannah Lee, J R Hamilton

Abstract

It has been 20 years since the discovery of the prototypical protease-activated receptor (PAR). In the time since this landmark work, significant advances have been made in our understanding of this family of four G protein-coupled receptors. Initially discovered and characterized in an attempt to determine the mechanism by which thrombin activates platelets, PARs have since been found to be widely expressed throughout the body, respond to multiple proteases, and to be involved in a vast array of physiological processes. Yet despite their wide-ranging expression, the function of PARs has been most extensively studied in the vascular system. In particular, the importance of PAR1 for platelet activation during arterial thrombosis has been thoroughly investigated and has led to the development of a host of PAR1 antagonists--two of which are currently in Phase 3 trials as antiplatelet agents. Given the impending clinical use of the first PAR antagonists, it is timely to review the physiological roles of PARs in cells of the blood and blood vessels, the development and experimental use of PAR antagonists in these systems, and the potential clinical application of these agents as therapeutics for vascular diseases.

References

Oct 1, 1992·The Journal of Clinical Investigation·N A NelkenS R Coughlin
Jul 1, 1992·Canadian Journal of Physiology and Pharmacology·I MuramatsuM D Hollenberg
Jan 1, 1992·Seminars in Thrombosis and Hemostasis·A B Malik, J W Fenton
Jan 1, 1987·Annual Review of Biochemistry·A G Gilman
Jun 1, 1995·Hypertension Research : Official Journal of the Japanese Society of Hypertension·P M Vanhoutte, C M Boulanger
Sep 27, 1994·Proceedings of the National Academy of Sciences of the United States of America·S NystedtJ Sundelin
Dec 1, 1994·Circulation Research·J N WilcoxT A Salam
Jan 15, 1996·The Biochemical Journal·R J GrandP W Grabham
Feb 1, 1996·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·K K Griendling, R W Alexander
Mar 1, 1996·The Journal of Experimental Medicine·G CirinoS R Stone
Jul 12, 1996·The Journal of Biological Chemistry·B D BlackhartR M Scarborough
Apr 26, 1996·International Journal of Cardiology·H I MagazineK D Srivastava
Jan 1, 1996·Seminars in Thrombosis and Hemostasis·C A McNamaraG K Owens
Dec 6, 1996·Journal of Medicinal Chemistry·M S BernatowiczS M Seiler
Feb 14, 1997·The Journal of Biological Chemistry·M MolinoL F Brass
Jun 1, 1997·Circulation Research·Q CapersW R Taylor
Jul 1, 1997·Journal of Vascular Research·K EmilssonJ Sundelin
Sep 18, 1997·The Journal of Clinical Investigation·C U CorveraN W Bunnett
Jan 22, 1998·Biochemical and Biophysical Research Communications·F BonoJ M Herbert
Apr 4, 1998·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·M R D'AndreaP Andrade-Gordon

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Citations

Jun 14, 2014·Vascular Pharmacology·Maria Adele Alberelli, Erica De Candia
Oct 25, 2012·Thrombosis and Haemostasis·Hannah Lee, Justin R Hamilton
Dec 18, 2013·Molecular Nutrition & Food Research·Min Soo KimYoung-Hee Kang
Jan 13, 2015·British Journal of Pharmacology·Mahmoud SaifeddineRithwik Ramachandran
Aug 15, 2015·Blood·Pat Metharom, Michael C Berndt
Nov 26, 2013·Thrombosis Research·Kazuya HosokawaIkuro Maruyama
Jan 26, 2018·Journal of Cardiovascular Development and Disease·Nathan A HollandDavid A Tulis
Sep 3, 2013·Expert Review of Proteomics·Joanna-Marie Howes
Apr 20, 2014·American Journal of Physiology. Gastrointestinal and Liver Physiology·Sung Yong EumMichal Toborek
Jan 29, 2016·International Journal of Molecular Medicine·Min JinJi-Fu Wei
Mar 11, 2016·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Kana MaruyamaSatomi Kagota
Aug 28, 2020·Thrombosis Research·Xu Han, Marvin T Nieman

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