Nitric oxide donors inhibit platelet spreading on surfaces coated with fibrinogen but not with fibronectin.
We have studied the effect of nitric oxide (NO) on the interaction of washed human platelets with fibrinogen or fibronectin adsorbed on glass. Platelet contacts were visualized by interference reflection microscopy at 37 degrees C in Tyrode's solution. The areas of spread platelets were measured, using digital video image processing techniques, at times up to 30 minutes after initial surface platelet contact. On fibrinogen spreading was inhibited by NO donors in the order of potency: S-nitroso-acetylpenicillamine > sodium nitroprusside > S-nitroso-glutathione. The inhibitory action of NO donors was prevented by Oxy-haemoglobin, confirming that this inhibition was due to the release of NO. In contrast, NO donors had virtually no effect on platelet spreading on fibronectin. Platelet adhesion to fibrinogen is mediated by GP IIb IIIa and the vitronectin receptor (VNR), while that to fibronectin is via GP IIb IIIa, VNR, Ic IIa and VLA-6. Our results thus indicate that NO inhibits adhesion mediated by GP IIb IIIa and/or VNR but not by the two other receptors. The mechanism of this receptor-specific inhibition of platelet adhesion remains to be elucidated.
Department of Anatomy & Developmental Biology, University College London, U.K.
T
T
Shahbazi
N
N
Jones
M W
MW
Radomski
M A
MA
Moro
D
D
Gingell
D000327:Adsorption; D001792:Blood Platelets / Q000648:ultrastructure; D048429:Cell Size; D005340:Fibrinogen; D005353:Fibronectins; D005898:Glass; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D026423:S-Nitroso-N-Acetylpenicillamine; D026422:S-Nitrosoglutathione
D005353:Fibronectins; D009603:Nitroso Compounds; D010108:Oxyhemoglobins; D010980:Platelet Membrane Glycoproteins; D009599:Nitroprusside; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D026423:S-Nitroso-N-Acetylpenicillamine; D005340:Fibrinogen; D005978:Glutathione; D010396:Penicillamine