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Antiplatelet Activity of KR-32558, a Novel Selective Sodium/hydrogen Exchanger-1 Inhibitor  

Lee, Mi-Yea (College of Social Sciences, Cheongju University)
Yun, Yeo-Pyo (College of Pharmacy, Chungbuk National University)
Publication Information
Journal of Food Hygiene and Safety / v.19, no.3, 2004 , pp. 161-166 More about this Journal
Abstract
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 ${\mu}g/ml$) with an $IC_{50}$ value of 85.9 ${\mu}M$, but with much weaker potency against aggregation induced by thapsigargin (0.5 ${\mu}M$) or A23187 (5 ${\mu}M$). And had no effect on platelet aggregation induced by arachidonic acid (100 ${\mu}M$), thrombin (0.05 U/ml) and U46619 (1 ${\mu}M$) up to 100 ${\mu}M$. KR-32558 completely inhibited the $[Ca^{2+}]_i$ mobilization induced by collagen at concentration of 100${\mu}iM$. Taken together, these observation suggest that KR-32558 selectively inhibited collagen-mediated platelet aggregation by blocking the cytoplasmic calcium mobilization in addition to NHE-1 inhibition.
Keywords
KR-32558; sodium-hydrogen exchanger-1; platelet aggregation; [Ca(2+)]i mobilization;
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