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Ticagrelor induces adenosine triphosphate release from human red blood cells.

Öhman, Jenny LU ; Kudira, Ramesh LU ; Albinsson, Sebastian LU ; Olde, Björn LU and Erlinge, David LU (2012) In Biochemical and Biophysical Research Communications 418(4). p.754-758
Abstract
RATIONALE: The novel P2Y(12) antagonist ticagrelor inhibits ADP-induced platelet aggregation more rapidly and more potently than clopidogrel. Clinical trials have revealed dyspnea and asymptomatic ventricular pauses as side effects of ticagrelor. The mechanism behind these side effects is not known, but it is plausible that they are mediated by adenosine.



OBJECTIVE: Ticagrelor is known to increase adenosine concentrations by inhibiting red blood cell reuptake, but the potency of this effect may be too low to fully explain the adenosine related effects. The purpose of the present study was to determine whether ticagrelor has other effects on red blood cells (RBCs) that could contribute to explain the pleiotropic effects... (More)
RATIONALE: The novel P2Y(12) antagonist ticagrelor inhibits ADP-induced platelet aggregation more rapidly and more potently than clopidogrel. Clinical trials have revealed dyspnea and asymptomatic ventricular pauses as side effects of ticagrelor. The mechanism behind these side effects is not known, but it is plausible that they are mediated by adenosine.



OBJECTIVE: Ticagrelor is known to increase adenosine concentrations by inhibiting red blood cell reuptake, but the potency of this effect may be too low to fully explain the adenosine related effects. The purpose of the present study was to determine whether ticagrelor has other effects on red blood cells (RBCs) that could contribute to explain the pleiotropic effects seen with ticagrelor treatment.



METHODS AND RESULTS: Using a luciferase-based bioluminescence assay, we studied ATP release in human blood. Human RBCs responded to ticagrelor in vitro by releasing substantial amounts of ATP in a dose-dependent manner (IC(50) 14μM). The rapid effect indicates release through membrane channels, which was supported by a depolarizing effect of ticagrelor and inhibition of ATP release by anion channel blockers.



CONCLUSION: In conclusion, our data show that, in vitro, ticagrelor can induce ATP release from human RBCs, which is subsequently degraded to adenosine. Further studies are warranted to determine what role this mechanism may play in the clinical effects of ticagrelor. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biochemical and Biophysical Research Communications
volume
418
issue
4
pages
754 - 758
publisher
Elsevier
external identifiers
  • WOS:000301332100029
  • PMID:22306816
  • Scopus:84857444798
ISSN
1090-2104
DOI
10.1016/j.bbrc.2012.01.093
language
English
LU publication?
yes
id
7aefef92-3b26-42fe-94ca-8067bcdcb4ad (old id 2367234)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22306816?dopt=Abstract
date added to LUP
2012-03-02 09:16:18
date last changed
2016-10-30 04:34:21
@misc{7aefef92-3b26-42fe-94ca-8067bcdcb4ad,
  abstract     = {RATIONALE: The novel P2Y(12) antagonist ticagrelor inhibits ADP-induced platelet aggregation more rapidly and more potently than clopidogrel. Clinical trials have revealed dyspnea and asymptomatic ventricular pauses as side effects of ticagrelor. The mechanism behind these side effects is not known, but it is plausible that they are mediated by adenosine.<br/><br>
<br/><br>
OBJECTIVE: Ticagrelor is known to increase adenosine concentrations by inhibiting red blood cell reuptake, but the potency of this effect may be too low to fully explain the adenosine related effects. The purpose of the present study was to determine whether ticagrelor has other effects on red blood cells (RBCs) that could contribute to explain the pleiotropic effects seen with ticagrelor treatment.<br/><br>
<br/><br>
METHODS AND RESULTS: Using a luciferase-based bioluminescence assay, we studied ATP release in human blood. Human RBCs responded to ticagrelor in vitro by releasing substantial amounts of ATP in a dose-dependent manner (IC(50) 14μM). The rapid effect indicates release through membrane channels, which was supported by a depolarizing effect of ticagrelor and inhibition of ATP release by anion channel blockers.<br/><br>
<br/><br>
CONCLUSION: In conclusion, our data show that, in vitro, ticagrelor can induce ATP release from human RBCs, which is subsequently degraded to adenosine. Further studies are warranted to determine what role this mechanism may play in the clinical effects of ticagrelor.},
  author       = {Öhman, Jenny and Kudira, Ramesh and Albinsson, Sebastian and Olde, Björn and Erlinge, David},
  issn         = {1090-2104},
  language     = {eng},
  number       = {4},
  pages        = {754--758},
  publisher    = {ARRAY(0x9ed6790)},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {Ticagrelor induces adenosine triphosphate release from human red blood cells.},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2012.01.093},
  volume       = {418},
  year         = {2012},
}