Original ArticlesRole of extracellular ATP metabolism in regulation of platelet reactivity☆,☆☆
Section snippets
Chemicals and reagents
Recombinant solCD39 was prepared as described previously.16 α-[32P]ATP and γ-[32P]ATP (3000 Ci/mmol, 10 mCi/mL of 50 mmol/L Tricine, pH 7.6) were obtained from NEN Life Science Products (Boston, Mass). α-[32P]ADP was prepared from α-[32P]ATP by means of enzymatic degradation with alkaline phosphatase (Promega, Madison, Wis) and separated with the use of paper electrophoresis on DEAE paper at pH 1.9, followed by elution.27 All other chemicals and reagents were obtained from Sigma Chemical Co (St
Results
ATP alone had no effect on platelet aggregation, even when doses as high as 50 μmol/L were added to human PRP (Fig 1).
Discussion
Control of circulating nucleotide levels is important in the maintenance of physiological nucleotide-mediated signaling processes. Such control is provided in part by endothelial cell CD39, which, in concert with prostacyclin and nitric oxide, primarily accounts for maintenance of blood fluidity.28, 29 Our results show that circulating ADP and ATP also can be efficiently hydrolyzed by a soluble enzyme in human plasma. In plasma, ATP was hydrolyzed directly to AMP without any significant
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Supported in part by National Institutes of Health grants R37-DA02475 (HHS), DK56424-02 (HDR), HL-46403 (AJM, MJB), HL-47073 (AJM, MJB), and NS-41462 (AJM, MJB); predoctoral fellowship F31-DA05862-01 from the National Institute on Drug Abuse (AVB); NIDA training grant DAO7274 from the National Institutes of Health (AVB); and merit review grants from the Department of Veterans Affairs (AJM, MJB, JHFD). We thank Charles R. Maliszewski, PhD, and colleagues (Immunex Corp, Seattle, Wash) for a generous gift of solCD39.
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Reprint requests: Hazel H. Szeto, MD, PhD, Department of Pharmacology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021; e-mail: [email protected].