Inhibition of platelet aggregation by S-nitroso-cysteine via cGMP-independent mechanisms: evidence of inhibition of thromboxane A2 synthesis in human blood platelets

FEBS Lett. 1999 Jan 15;442(2-3):162-6. doi: 10.1016/s0014-5793(98)01633-0.

Abstract

S-Nitroso-cysteine (SNC), a putative endothelium-derived relaxing factor, potently inhibited collagen- and arachidonic acid-induced platelet aggregation (IC50=100 nM) and thromboxane A2 (TxA2) synthesis of human blood platelets. ODQ, a selective inhibitor of the soluble guanylyl cyclase, inhibited SNC-induced formation of cGMP but did not reverse inhibition by SNC of collagen- and arachidonic acid-induced platelet aggregation. Combination of ODQ with SQ-29548, a specific platelet TxA2 receptor antagonist, did not modify the antiaggregatory action of SNC. Our study shows that SNC inhibits platelet aggregation by cGMP-independent mechanisms that may involve inhibition of TxA2 synthesis in human platelets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonic Acid / pharmacology
  • Aspirin / pharmacology
  • Blood Platelets / metabolism*
  • Bridged Bicyclo Compounds, Heterocyclic
  • Collagen / pharmacology
  • Cyclic GMP / metabolism*
  • Cysteine / analogs & derivatives*
  • Cysteine / metabolism
  • Cysteine / pharmacology
  • Fatty Acids, Unsaturated
  • Glutathione / analogs & derivatives
  • Glutathione / metabolism
  • Guanylate Cyclase / antagonists & inhibitors
  • Humans
  • Hydrazines / pharmacology
  • Inhibitory Concentration 50
  • Nitric Oxide / metabolism
  • Nitrites / metabolism
  • Nitroprusside / pharmacology
  • Nitroso Compounds / metabolism
  • Nitroso Compounds / pharmacology*
  • Oxadiazoles / pharmacology
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / metabolism
  • Platelet Aggregation Inhibitors / pharmacology*
  • Quinoxalines / pharmacology
  • S-Nitrosoglutathione
  • S-Nitrosothiols*
  • Thromboxane A2 / biosynthesis*

Substances

  • 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one
  • Bridged Bicyclo Compounds, Heterocyclic
  • Fatty Acids, Unsaturated
  • Hydrazines
  • Nitrites
  • Nitroso Compounds
  • Oxadiazoles
  • Platelet Aggregation Inhibitors
  • Quinoxalines
  • S-Nitrosothiols
  • Nitroprusside
  • Arachidonic Acid
  • Nitric Oxide
  • S-Nitrosoglutathione
  • Thromboxane A2
  • SQ 29548
  • Collagen
  • S-nitrosocysteine
  • Guanylate Cyclase
  • Glutathione
  • Cyclic GMP
  • Cysteine
  • Aspirin