Inhibition of platelet adhesion to collagen by cGMP-elevating agents.
In the present study, we examined the effects and action mechanisms of cGMP-elevating agents on platelet adhesion to collagen fiber. YC-1, a nitric oxide (NO)-independent activator of soluble guanylate cyclase, inhibited both initial and long-term platelet adhesion to collagen, and the inhibitory effect was potentiated by dipyridamole, a selective inhibitor of cGMP-specific phosphodiesterase. Sodium nitroprusside (SNP), a NO-donor, and 8-bromo-cGMP also inhibited the initial platelet adhesion, but inhibited long-term adhesion only in the presence of dipyridamole. Collagen-induced intracellular Ca2+ mobilization and actin polymerization were prevented by YC-1, SNP and 8-bromo-cGMP. Since blockade of Ca2+ mobilization and actin polymerization caused by collagen led to decrease of platelet adhesion, we suggest that the inhibitory activity of cGMP-elevating agents on the adhesion of platelets to collagen is resulting from interference of these signaling pathways.
Wu
C C
CC
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
Ko
F N
FN
Teng
C M
CM
D000199:Actins / Q000378:metabolism; D000328:Adult; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D003094:Collagen; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007191:Indazoles / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology
D000199:Actins; D007191:Indazoles; D010975:Platelet Aggregation Inhibitors; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D003094:Collagen; D006152:Cyclic GMP; D002118:Calcium