Ticlopidine in Its Prodrug Form Is a Selective Inhibitor of Human NTPDase1

Figure 5

Inhibition of NTPDase1 ATPase activity in human tissues by ticlopidine. Enzyme histochemistry was performed on serial sections with the substrate ATP at a final concentration of 200 μM in the presence or absence of 100 μM ticlopidine. In both tissues (liver and pancreas) NTPDase1 ATPase activity is located in endothelial cells of all blood vessels including capillaries and sinusoids as well as in smooth muscle cells of arteries and in resident macrophages (Küpffer cells in the liver). In addition, in the pancreas NTPDase1 is also expressed at the luminal surface of acinar cells and in zymogen granules. The ATPase activity is seen as a brown precipitate and is completely absent in presence of ticlopidine. Nuclei were counterstained with haematoxylin. Scale bar = 50 μm. V = vein; = Langerhans islet; arrows = Küpffer cells.