Summary
Pentamidine was previously shown to act on glycoprotein (GP) Ilb/IIIa (Cox et al.,
Thromb Haemost 1992; 68: 731). In this paper we study the effect of pentamidine on
other RGD-dependent receptors. In a cell adhesion assay, pentamidine was 500 times
more potent than RGDS at inhibiting platelet adhesion to fibrinogen. While RGDS inhibited
platelet adhesion to fibronectin, endothelial cell adhesion to vitronectin or fibronectin,
293 cell adhesion to vitronectin, IMR 32 cell adhesion to fibronectin and C32 cell
adhesion to vitronectin; pentamidine failed to inhibit these interactions at doses
as high as 1 mM. Resting platelets fixed in the presence of 1 mM RGDS had increased
binding of fibrinogen, i.e., RGDS activated GPIMIIa, while pentamidine at 100 ΜM had
no effect. Similarly, RGDS induced the binding of an anti-LIBS monoclonal antibody,
while pentamidine had no effect. Pentamidine partially, but significantly, inhibited
lysosome and a-granule release induced by the thrombin agonist peptide, while RGDS
had no effect. Neither pentamidine nor RGDS affected ADP-induced Ca2+ influx. Pentamidine had no effect on ADP-induced intracellular pH changes while RGDS
prevented the pH from returning to normal. Thus, pentamidine is a non-peptide GPIIb/IIIa
antagonist that is non-activating and is specific for GPIIb/IIIa.
