10.1021/jm000020b.s001
Fernand-Pierre Gendron
Fernand-Pierre
Gendron
Efrat Halbfinger
Efrat
Halbfinger
Bilha Fischer
Bilha
Fischer
Martine Duval
Martine
Duval
Pédro D'Orléans-Juste
Pédro
D'Orléans-Juste
Adrien R. Beaudoin
Adrien R.
Beaudoin
Novel Inhibitors of Nucleoside Triphosphate Diphosphohydrolases: Chemical
Synthesis and Biochemical and Pharmacological Characterizations
American Chemical Society
2000
10 μ M
P 2X effect
Pharmacological Characterizations
nucleoside triphosphate diphosphohydrolase
purinergic receptors
NTPDase inhibitors
NTPDase inhibitor
Novel Inhibitors
P 2Y 1
EC
ATP analogues
nonhydrolyzable analogue
K i
turkey erythrocytes
enzyme source
guinea pig
purine ring
blood pressure variations
precontracted vessel
2000-05-11 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Novel_Inhibitors_of_Nucleoside_Triphosphate_Diphosphohydrolases_Chemical_Synthesis_and_Biochemical_and_Pharmacological_Characterizations/3679458
To elucidate the physiological role played by nucleoside triphosphate diphosphohydrolase
(NTPDase; EC 3.6.1.5), adenine nucleotide analogues, modified on the purine ring, have been
synthesized and tested as potential inhibitors. Resistance of ATP analogues to hydrolysis and
their potency as NTPDase inhibitors were evaluated. For this purpose, a particulate fraction
isolated from bovine spleen was used as the enzyme source. Among the synthesized analogues,
8-thiobutyladenosine 5‘-triphosphate (8-BuS-ATP) was found to be the most effective nonhydrolyzable competitive inhibitor, with an estimated <i>K</i><sub>i</sub> of 10 μM. This nonhydrolyzable analogue
did not exert any P2X-receptor-mediated effect on endothelium-denuded blood vessels, from
the guinea pig mesenteric bed. In agreement with this observation, infusion of the analogue
did not cause any significant blood pressure variations of the precontracted vessel. Because in
previous studies on isolated turkey erythrocytes and rat astrocytes 8-BuS-ATP was not able
to trigger any P2Y<sub>1</sub>-receptor-mediated effect, it therefore appears that this NTPDase inhibitor
does not interfere with purinergic receptors.