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Extracellular nucleotides ATP and UTP induce a marked acute release of tissue-type plasminogen activator in vivo in man

Hrafnkelsdottir, Thórdís; Erlinge, David LU and Jern, Sverker (2001) In Thrombosis and Haemostasis 85(5). p.875-881
Abstract
Extracellular nucleotides such as ATP and UTP are released by activation of platelets and ischemic tissue injury. The aim of the present study was to investigate whether ATP and UTP can induce acute tPA release from the vascular endothelium in vivo. Nine healthy subjects were studied in a perfused-forearm model during stepwise intraarterial infusions of ATP and UTP (10-200 nmol/min), and UTP during inhibition of prostanoid and NO synthesis by indomethacin and L-NMMA. ATP and UTP induced a similar and marked stimulation of forearm tPA release which increased 11- and 18-fold above baseline (p < or =0.01 for both) in conjunction with pronounced vasodilation. Neither the acute tPA release nor the vasodilation could be abrogated by NO and... (More)
Extracellular nucleotides such as ATP and UTP are released by activation of platelets and ischemic tissue injury. The aim of the present study was to investigate whether ATP and UTP can induce acute tPA release from the vascular endothelium in vivo. Nine healthy subjects were studied in a perfused-forearm model during stepwise intraarterial infusions of ATP and UTP (10-200 nmol/min), and UTP during inhibition of prostanoid and NO synthesis by indomethacin and L-NMMA. ATP and UTP induced a similar and marked stimulation of forearm tPA release which increased 11- and 18-fold above baseline (p < or =0.01 for both) in conjunction with pronounced vasodilation. Neither the acute tPA release nor the vasodilation could be abrogated by NO and prostanoid synthesis inhibition. The similar effect of ATP and UTP suggests that P2Y rather than adenosine receptors mediate the response. Release of extracellular nucleotides in ischemic tissue may induce a pronounced activation of the endogenous fibrinolytic system. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Thrombosis and Haemostasis
volume
85
issue
5
pages
875 - 881
publisher
F K Schattauer Verlag Gmbh
external identifiers
  • pmid:11372682
  • scopus:0035020962
ISSN
0340-6245
language
English
LU publication?
yes
id
1f51b749-ff92-41ad-bca0-dbc3fc0cf7b2 (old id 1121352)
date added to LUP
2008-06-30 15:36:13
date last changed
2018-01-07 09:22:16
@article{1f51b749-ff92-41ad-bca0-dbc3fc0cf7b2,
  abstract     = {Extracellular nucleotides such as ATP and UTP are released by activation of platelets and ischemic tissue injury. The aim of the present study was to investigate whether ATP and UTP can induce acute tPA release from the vascular endothelium in vivo. Nine healthy subjects were studied in a perfused-forearm model during stepwise intraarterial infusions of ATP and UTP (10-200 nmol/min), and UTP during inhibition of prostanoid and NO synthesis by indomethacin and L-NMMA. ATP and UTP induced a similar and marked stimulation of forearm tPA release which increased 11- and 18-fold above baseline (p &lt; or =0.01 for both) in conjunction with pronounced vasodilation. Neither the acute tPA release nor the vasodilation could be abrogated by NO and prostanoid synthesis inhibition. The similar effect of ATP and UTP suggests that P2Y rather than adenosine receptors mediate the response. Release of extracellular nucleotides in ischemic tissue may induce a pronounced activation of the endogenous fibrinolytic system.},
  author       = {Hrafnkelsdottir, Thórdís and Erlinge, David and Jern, Sverker},
  issn         = {0340-6245},
  language     = {eng},
  number       = {5},
  pages        = {875--881},
  publisher    = {F K Schattauer Verlag Gmbh},
  series       = {Thrombosis and Haemostasis},
  title        = {Extracellular nucleotides ATP and UTP induce a marked acute release of tissue-type plasminogen activator in vivo in man},
  volume       = {85},
  year         = {2001},
}