Inhibitory effect of prostacyclin and nitroprusside on type IIB von Willebrand factor-promoted platelet activation.
Von Willebrand disease (vWD) of type IIB is a hereditary haemorrhagic disorder characterised by an excessive interaction of von Willebrand factor (vWF) with the platelet receptor GPIb which promotes platelet activation and aggregation through a phospholipase A2-mediated release of arachidonic acid. The present report shows that prostacyclin and nitroprusside, vasodilator-compounds that enhance the cAMP and cGMP concentration respectively, cause a drastic inhibition of the type IIB vWF-induced platelet responses including increase of cytosolic Ca2+ concentration, phosphorylation of pleckstrin (47 kDa) and myosin light chain (20 kDa), secretion of ATP and serotonin, and aggregation parallel to a decrease of arachidonic acid release. Type IIB vWF also elicits tyrosine phosphorylation of proteins with apparent molecular mass of 60, 74, 82 and 130 kDa. Prostacyclin, which induces per se tyrosine-phosphorylation of proteins of about 38 and 45 kDa, inhibits drastically the type IIB vWF-promoted tyrosine-phosphorylation of the 74 kDa protein while inhibits slightly that of 60 kDa band. The protein tyrosine-kinase inhibitor genistein causes a little decrease in the type IIB vWF-induced release of arachidonic acid. It is concluded that the inhibition exerted by prostacyclin and nitroprusside on type IIB vWF-elicited platelet activation seems to be largely ascribable to prevention of the phospholipase A2 activation with the ensuing decrease of the subsequent protein tyrosine phosphorylation.
Francesconi
M
M
Department of Biological Chemistry, University of Padova, Italy.
Casonato
A
A
Pagan
S
S
Donella-Deana
A
A
Pontara
E
E
Girolami
A
A
Deana
R
R
D011464:Epoprostenol / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D009599:Nitroprusside / Q000494:pharmacology* / Q000627:therapeutic use; D010741:Phospholipases A / Q000097:blood; D054467:Phospholipases A2; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D014842:von Willebrand Diseases / Q000097:blood / Q000188:drug therapy*; D014841:von Willebrand Factor / Q000494:pharmacology* / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D014841:von Willebrand Factor; D009599:Nitroprusside; D011464:Epoprostenol; D010741:Phospholipases A; D054467:Phospholipases A2