PMID: 11919550Mar 29, 2002Paper

Role of a novel soluble nucleotide phospho-hydrolase from sheep plasma in inhibition of platelet reactivity: hemostasis, thrombosis, and vascular biology

The Journal of Laboratory and Clinical Medicine
Alex V BirkHazel H Szeto

Abstract

Ecto- and exoenzymes that metabolize extracellular adenosine diphosphate (ADP), the major promoter of platelet activation and recruitment, are of potential clinical importance because they can metabolically prevent excessive thrombus growth. An ecto-ADPase (CD39, NTPDase1) has been identified on endothelial cells. We demonstrate that ADP and adenosine triphosphate (ATP) are rapidly metabolized to adenosine monophosphate (AMP) in sheep plasma at pH 7.4. This hydrolysis is sensitive to P(1), P(5)-di-(adenosine-5') pentaphosphate (Ap(5)A), and ethylene glycol bis (beta-aminoethyl ether) - N, N, N(-), N(-) tetra-acetate (EGTA) but insensitive to tetramisole (an alkaline phosphatase inhibitor). A specific phosphodiesterase substrate, p -nitrophenol-5'-thymidine monophosphate (TMP) (p -Nph-5'-TMP), was readily hydrolyzed in sheep plasma at a rate of approximately 0.25 nmol/min/mg protein, and this hydrolysis was inhibited by ADP, ATP, and Ap(5)A. Furthermore, 200-fold purified p -Nph-5'-TMP-hydrolyzing activity also hydrolyzed ATP and ADP directly to AMP. When ADP was preincubated in plasma, its ability to induce platelet aggregation was inhibited in a time-dependent manner. This effect was abolished by Ap(5)A. The inhibitory effects...Continue Reading

Citations

Nov 14, 2012·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Jamile F GonçalvesMaria Rosa C Schetinger
Mar 22, 2003·The Journal of Pharmacology and Experimental Therapeutics·Aaron J MarcusRoberto Levi
Jul 1, 2009·British Journal of Pharmacology·Vera JankowskiJoachim Jankowski
Oct 22, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Alex V BirkHazel H Szeto
May 23, 2009·Inhalation Toxicology·G R ThoméM R C Schetinger
Sep 22, 2012·Blood·Ronald A AlbrightDemetrios T Braddock
Jun 15, 2007·The Journal of Pharmacology and Experimental Therapeutics·Ulrich SchaeferRoberto Levi
Sep 25, 2002·The Journal of Laboratory and Clinical Medicine·Alex V BirkHazel H Szeto
Apr 20, 2004·Life Sciences·Jean Pierre OsesJoão José Freitas Sarkis
Jan 17, 2012·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Daniela ZaniniMaria Rosa Chitolina Schetinger

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