Involvement of disulfide-sulfhydryl interaction in anti-platelet actions of KF4939.
We studied on the role of an intramolecular disulfide bond of KF4939 in its anti-platelet actions by using rabbit platelets. The inhibitions of aggregation of platelet-rich plasma (PRP) and washed platelets, and of malondialdehyde production in thrombin-stimulated platelets by KF4939 were counteracted by pretreatment with sulfhydryl compounds, glutathione, 1-cysteine and dithiothreitol. A reduced compound of KF4939 (Red-KF4939) showed nearly equal anti-aggregating activities to those of KF4939 in PRP, it, however, showed low activities to inhibit platelet aggregation and thrombin -stimulated malondialdehyde production in washed platelet suspensions. In addition, the anti-aggregating action of Red-KF4939 was counteracted by pretreatment with sulfhydryl compounds, similarly to that of KF4939. Furthermore, when platelets were treated with KF4939, a significant decrease of protein-bound sulfhydryl groups was observed. We may conclude from these results that the intramolecular disulfide bond plays an essential role in anti-platelet actions of KF4939 and the interaction of the disulfide bond with protein-bound sulfhydryl groups may be involved in the mechanism of anti-platelet actions of KF4939.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism; D004220:Disulfides / Q000494:pharmacology*; D004347:Drug Interactions; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D013438:Sulfhydryl Compounds / Q000097:blood / Q000494:pharmacology*
D001549:Benzamides; D004220:Disulfides; D013438:Sulfhydryl Compounds; C037861:2,2'-dithiobis(N-2-hydroxypropylbenzamide)