We investigated the antiplatelet effect of a newly synthesized guanidine derivative KR-32558, a sodium-hydrogen exchanger-1 (NHE-1) inhibitor, together with the elucidation of the possible mechanisms of action. KR-32558 concentration -dependently inhibited the aggregation of washed rabbit platelets induced by collagen (10 μg/ml) with an IC_(50) value of 85.9 μM, but with much weaker potency against aggregation induced by thapsigargin (0.5 μM) or A23187 (5 μM). And had no effect on platelet aggregation induced by arachidonic acid (100 μM), thrombin (0.05 U/ml) and U46619 (1 μM) up to 100 μM. KR-32558 completely inhibited the [Ca^(2+)] mobilization induced by collagen at concentration of 100μiM. Taken together, these observations suggest that KR-32558 selectively inhibited collagen-mediated platelet aggregation by blocking the cytoplasmic calcium mobilization in addition to NHE-1 inhibition.

• Lee, Mi-Yea
• Yun, Yeo-Pyo