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This Article Full Text Full Text (PDF) All Versions of this Article: 579/2/553    most recent jphysiol.2006.119453v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yegutkin, G. G. Articles by González-Alonso, J. Search for Related Content PubMed PubMed Citation Articles by Yegutkin, G. G. Articles by González-Alonso, J. Related Collections Integrative

¹ MediCity Research Laboratory, University of Turku and National Public Health Institute, Turku, Finland
² The Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Denmark
³ Centre for Sports Medicine and Human Performance, Brunel University, Uxbridge, Middlesex, UK

Extracellular ATP and ADP trigger vasodilatatory and prothrombotic signalling events in the vasculature. Here, we tested the hypothesis that nucleotide turnover is activated in the bloodstream of exercising humans thus contributing to the enhanced platelet reactivity and haemostasis. Right atrial, arterial and venous blood samples were collected from endurance-trained athletes at rest, during submaximal and maximal cycle ergometer exercise, and after early recovery. ATP-specific bioluminescent assay, together with high-performance liquid chromatographic analysis, revealed that plasma ATP and ADP concentrations increased up to 2.5-fold during maximal exercise. Subsequent flow cytometric analysis showed that plasma from exercising subjects significantly up-regulated the surface expression of P-selectin in human platelets and these prothrombotic effects were diminished after scavenging plasma nucleotides with exogenous apyrase. Next, using thin layer chromatographic assays with [-³²P]ATP and ³H/¹⁴C-labelled nucleotides, we showed that two soluble nucleotide-inactivating enzymes, nucleotide pyrophosphatase/phosphodiesterase and nucleoside triphosphate diphosphohydrolase, constitutively circulate in human bloodstream. Strikingly, serum nucleotide pyrophosphatase and hydrolase activities rose during maximal exercise by 20–25 and 80–100%, respectively, and then declined after 30 min recovery. Likewise, soluble nucleotidases were transiently up-regulated in the venous blood of sedentary subjects during exhaustive exercise. Human serum also contains 5'-nucleotidase, adenylate kinase and nucleoside diphosphate (NDP) kinase; however, these activities remain unchanged during exercise. In conclusion, intravascular ADP significantly augments platelet activity during strenuous exercise and these prothrombotic responses are counteracted by concurrent release of soluble nucleotide-inactivating enzymes. These findings provide a novel insight into the mechanisms underlying the enhanced risk of occlusive thrombus formation under exercising conditions.

(Received 17 August 2006; accepted after revision 30 December 2006; first published online 4 January 2007)
Corresponding author G. G. Yegutkin: MediCity, Turku University, Tykistökatu 6A, 20520 Turku, Finland. Email: genyeg{at}utu.fi

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