Platelet activation by diacylglycerol or ionomycin is inhibited by nitroprusside.
Experiments were performed to elucidate the role of cyclic guanosine monophosphate (cGMP) on platelet activation induced by protein kinase C (PKC) activators and calcium ionophore. Human platelets were pretreated with acetylsalicylic acid and with hirudin and apyrase. Aggregation and ATP secretion in response to the PKC activators 4 beta-phorbol 12-myristate 13-acetate (PMA) and 1-oleoyl 2-acetylglycerol (OAG) were inhibited by the nitrovasodilator sodium nitroprusside (SNP), an activator of guanylate cyclase, and by 8-bromo-cyclic GMP (8-Br-cGMP). The experiments were performed in the presence of M&B 22948, an inhibitor of cGMP phosphodiesterase. SNP and 8-Br-cGMP also inhibited platelet aggregation and secretion evoked by the ionophore ionomycin. In fura-2 loaded platelets SNP did not affect basal cytosolic Ca2+ level nor the rise induced by low concentrations of ionomycin, both in the presence and absence of extracellular Ca2+. The phosphorylation of the 47 and 20 kDa protein induced by ionomycin or PMA were not significantly decreased by SNP or 8-Br-cGMP. The present results suggest that cGMP is able to inhibit both the PKC and the Ca(2+)-dependent pathways leading to platelet activation by interfering, similarly to cAMP, with processes following protein phosphorylation, close to the effector systems.
Doni
M G
MG
Institute of Human Physiology, Faculty of Medicine and Surgery, University of Padova, Italy.
Deana
R
R
Padoin
E
E
Ruzzene
M
M
Alexandre
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D004075:Diglycerides / Q000494:pharmacology*; D015759:Ionomycin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology*; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D015759:Ionomycin; C038237:1-oleoyl-2-acetylglycerol; D000255:Adenosine Triphosphate; D006152:Cyclic GMP; D013755:Tetradecanoylphorbol Acetate