A novel role for phospholipase D as an endogenous negative regulator of platelet sensitivity

Cellular Signalling
Margitta ElversKnut Fälker

Abstract

Platelet aggregation, secretion and thrombus formation play a critical role in primary hemostasis to prevent excessive blood loss. On the other hand, uncontrolled platelet activation leads to pathological thrombus formation resulting in myocardial infarction or stroke. Stimulation of heterotrimeric G-proteins by soluble agonists or immunoreceptor tyrosine based activation motif-coupled receptors that interact with immobilized ligands such as the collagen receptor glycoprotein (GP) VI lead to the activation of phospholipases that cleave membrane phospholipids to generate soluble second messengers. Platelets contain the phospholipases (PL) D1 and D2 which catalyze the hydrolysis of phosphatidylcholine to generate the second messenger phosphatidic acid (PA). The production of PA is abrogated by primary alcohols that have been widely used for the analysis of PLD-mediated processes. However, it is not clear if primary alcohols effectively reduce PA generation or if they induce PLD-independent cellular effects. In the present study we made use of the specific PLD inhibitor 5-fluoro-2-indolyl des-chlorohalopemide (FIPI) and show for the first time, that FIPI enhances platelet dense granule secretion and aggregation of human platelets....Continue Reading

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Citations

Jan 21, 2014·Biochimica Et Biophysica Acta·Sarah A ScottH Alex Brown
Oct 7, 2015·Scientific Reports·Mohamed Raafet AmmarNicolas Vitale
Sep 15, 2012·Journal of Thrombosis and Haemostasis : JTH·I ThielmannB Nieswandt
Apr 14, 2017·American Journal of Physiology. Cell Physiology·Sascha GeuePatrick Münzer
Sep 18, 2013·The Journal of Pharmacology and Experimental Therapeutics·Elke C G JacksonArchie McNicol
Nov 18, 2018·Journal of Clinical Medicine·Wan Jung LuJoen Rong Sheu
May 7, 2020·International Journal of Molecular Sciences·Aglaia Maria KloseMargitta Elvers

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