Inhibition of vascular ectonucleotidase activities by the pro-drugs ticlopidine and clopidogrel favours platelet aggregation.

ABSTRACT:

Background and purpose

After conversion to their active forms by the liver, ticlopidine and clopidogrel exert antiplatelet effects through irreversible inhibition of the P2Y₁₂ receptor. Concentrations of nucleotides such as ADP, the physiological agonist at platelet P2Y₁ and P2Y₁₂ receptors, are regulated by vascular ectonucleotidases, mainly nucleoside triphosphate diphosphohydrolase (NTPDase)1 and ecto-5'-nucleotidase. Here we evaluate the effect of these pro-drugs on vascular ectonucleotidase activity and on the natural function of these enzymes in regulating platelet aggregation.

Experimental approach

Nucleotidase assays were performed by HPLC and by P(i) determination, using human umbilical vein endothelial cells (HUVEC) and protein extracts from transfected COS-7 cells

SUBMITTER: Lecka J 

PROVIDER: S-EPMC2998694 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature