Further insights into the anti-aggregating activity of NMDA in human platelets

British Journal of Pharmacology
F FranconiA Tagliamonte

Abstract

1. In the present study the effect of N-methyl-D-aspartate (NMDA) on thromboxane B2 synthesis and on [Ca2+]i was studied in human platelets. 2. NMDA (10(-7) M) completely inhibited the synthesis of thromboxane B2 from exogenous arachidonic acid (AA), while it did not interfere with the aggregating effect of the thromboxane A2 receptor agonist U-46619. 3. NMDA (0.1 microM - 10 microM) dose-dependently increased intracellular calcium in washed platelets preloaded with fura 2 AM, and this effect was not additive with that of AA. 4. NMDA shifted the dose-response curve of AA to the right. At the highest AA concentrations platelet aggregation was not inhibited. 5. The antiaggregating effect of NMDA was not antagonized by N(G)-monomethyl-L-arginine (L-NMMA), a nitric oxide synthase (NOS) inhibitor. 6. Finally, NMDA (0.01 nM - 100 nM) associated with either aspirin or indomethacin significantly potentiated the antiaggregating activity of both cyclo-oxygenase inhibitors. 7. It was concluded that NMDA is a potent inhibitor of platelet aggregation and thromboxane B2 synthesis in human platelet rich plasma (PRP).

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Citations

May 23, 2001·Thrombosis Research·F FranconiA Tagliamonte
Apr 3, 2001·Trends in Pharmacological Sciences·T M Skerry, P G Genever
Aug 25, 2012·The Journal of Biological Chemistry·Amit S Korde, William F Maragos
Feb 20, 2008·The Journal of Experimental Medicine·Craig N MorrellCharles J Lowenstein
Feb 22, 2012·Biochemistry. Biokhimii︠a︡·A A BoldyrevE A Vladychenskaya
Dec 11, 2007·Toxicology in Vitro : an International Journal Published in Association with BIBRA·V C Borges, C W Nogueira
Dec 26, 2006·The International Journal of Biochemistry & Cell Biology·Gary J SpencerPaul G Genever
Jun 30, 2012·Journal of Thrombosis and Haemostasis : JTH·M P Mahaut-Smith
Feb 28, 2006·Psychiatry Research·Carlos A M do NascimentoJoão B T Rocha
Sep 3, 2013·The International Journal of Biochemistry & Cell Biology·Ludmila A Kasatkina, Tatiana A Borisova
Mar 7, 2014·Thrombosis Research·Maggie L Kalev-ZylinskaChristopher M Ward
Jun 25, 2016·Trends in Pharmacological Sciences·Adam D Hogan-Cann, Christopher M Anderson
May 10, 2005·British Journal of Pharmacology·Barbara BegniCarlo Ferrarese
Mar 22, 2003·Blood·Ian S HitchcockPaul G Genever
Apr 6, 2017·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Vasco BrancoCristina Carvalho
Jul 7, 2020·Frontiers in Physiology·Maggie L Kalev-ZylinskaAnna Bogdanova
Dec 23, 2003·European Journal of Biochemistry·Eiichi HinoiYukio Yoneda
Dec 8, 2020·Platelets·Maggie L Kalev-ZylinskaAnna Y Bogdanova
Dec 9, 2004·Chemical Reviews·Cristina W NogueiraJoão B T Rocha

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