YC-1 potentiates the antiplatelet effect of hydrogen peroxide via sensitization of soluble guanylate cyclase.
In the present study, we showed that 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), a nitric oxide (NO)-independent activator of soluble guanylate cyclase, could potentiate H2O2-induced inhibition of platelet aggregation and increase of platelet cGMP levels. The synergistic effect of YC-1 and H2O2 on platelet aggregation and increases of cGMP were almost completely prevented by catalase and a selective soluble guanylate cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), or partially attenuated by the hydroxyl radical scavenger mannitol. In contrast, superoxide dismutase failed to influence H2O2/YC-1-induced inhibition of aggregation. Furthermore, YC-1 could enhance the activation of soluble guanylate cyclase caused by FeSO4/H2O2 and, this effect was prevented markedly by mannitol. These results suggest that YC-1 may enhance the antiaggregatory effect of H2O2 via the sensitization of platelet soluble guanylate cyclase. In addition, this phenomenon is, at least in part, dependent on H2O2-derived hydroxyl radical.
Wu
C C
CC
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
Kuo
S C
SC
Lee
F Y
FY
Teng
C M
CM
D000975:Antioxidants / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D002374:Catalase / Q000097:blood / Q000378:metabolism; D006152:Cyclic GMP / Q000096:biosynthesis; D005949:Glucose Oxidase / Q000097:blood; D005979:Glutathione Peroxidase / Q000097:blood / Q000378:metabolism; D006162:Guanylate Cyclase / Q000097:blood / Q000378:metabolism*; D006490:Hemostatics / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology*; D008353:Mannitol / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D000975:Antioxidants; D006490:Hemostatics; D007191:Indazoles; D010975:Platelet Aggregation Inhibitors; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D008353:Mannitol; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D013917:Thrombin; D006162:Guanylate Cyclase; D006152:Cyclic GMP