Ticlopidine in Its Prodrug Form Is a Selective Inhibitor of Human NTPDase1
Joint Authors
Sévigny, Jean
Lecka, Joanna
Fausther, Michel
Künzli, Beat
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-08-11
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Nucleoside triphosphate diphosphohydrolase-1 (NTPDase1), like other ectonucleotidases, controls extracellular nucleotide levels and consequently their (patho)physiological responses such as in thrombosis, inflammation, and cancer.
Selective NTPDase1 inhibitors would therefore be very useful.
We previously observed that ticlopidine in its prodrug form, which does not affect P2 receptor activity, inhibited the recombinant form of human NTPDase1 ( K i = 14 μM).
Here we tested whether ticlopidine can be used as a selective inhibitor of NTPDase1.
We confirmed that ticlopidine inhibits NTPDase1 in different forms and in different assays.
The ADPase activity of intact HUVEC as well as of COS-7 cells transfected with human NTPDase1 was strongly inhibited by 100 µM ticlopidine, 99 and 86%, respectively.
Ticlopidine (100 µM) completely inhibited the ATPase activity of NTPDase1 in situ as shown by enzyme histochemistry with human liver and pancreas sections.
Ticlopidine also inhibited the activity of rat and mouse NTPDase1 and of potato apyrase.
At 100 µM ticlopidine did not affect the activity of human NTPDase2, NTPDase3, and NTPDase8, nor of NPP1 and NPP3.
Weak inhibition (10–20%) of NTPDase3 and -8 was observed at 1 mM ticlopidine.
These results show that ticlopidine is a specific inhibitor of NTPDase1 that can be used in enzymatic and histochemistry assays.
American Psychological Association (APA)
Lecka, Joanna& Fausther, Michel& Künzli, Beat& Sévigny, Jean. 2014. Ticlopidine in Its Prodrug Form Is a Selective Inhibitor of Human NTPDase1. Mediators of Inflammation،Vol. 2014, no. 2014, pp.1-8.
https://search.emarefa.net/detail/BIM-1043637
Modern Language Association (MLA)
Lecka, Joanna…[et al.]. Ticlopidine in Its Prodrug Form Is a Selective Inhibitor of Human NTPDase1. Mediators of Inflammation No. 2014 (2014), pp.1-8.
https://search.emarefa.net/detail/BIM-1043637
American Medical Association (AMA)
Lecka, Joanna& Fausther, Michel& Künzli, Beat& Sévigny, Jean. Ticlopidine in Its Prodrug Form Is a Selective Inhibitor of Human NTPDase1. Mediators of Inflammation. 2014. Vol. 2014, no. 2014, pp.1-8.
https://search.emarefa.net/detail/BIM-1043637
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1043637