Inhibitory Effect of Prostacyclin and Nitroprusside on Type IIB von Willebrand Factor-promoted Platelet Activation

Mariangela Francesconi; Alessandra Casonato; Stefano Pagan; Arianna Donella-Deana; Elena Pontara; Antonio Girolami; Renzo Deana

doi:10.1055/s-0038-1650601

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1996; 76(03): 469-474
DOI: 10.1055/s-0038-1650601

Original Article

Schattauer GmbH Stuttgart

Inhibitory Effect of Prostacyclin and Nitroprusside on Type IIB von Willebrand Factor-promoted Platelet Activation

Mariangela Francesconi

The Department of Biological Chemistry and Unit for the Study of Biomembranes of C.N.R, Italy

,

Alessandra Casonato

¹The institute of Medical Semeiotics and Fourth Chair of Internal Medicine, University of Padova, Italy

,

Stefano Pagan

The Department of Biological Chemistry and Unit for the Study of Biomembranes of C.N.R, Italy

,

Arianna Donella-Deana

The Department of Biological Chemistry and Unit for the Study of Biomembranes of C.N.R, Italy

,

Elena Pontara

¹The institute of Medical Semeiotics and Fourth Chair of Internal Medicine, University of Padova, Italy

,

Antonio Girolami

¹The institute of Medical Semeiotics and Fourth Chair of Internal Medicine, University of Padova, Italy

,

Renzo Deana

The Department of Biological Chemistry and Unit for the Study of Biomembranes of C.N.R, Italy

› Author Affiliations

Abstract

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Summary

Von Willebrand disease (vWD) of type IIB is a hereditary haemorragic 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, vaso-dilator-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-phosphoryla-tion 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

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References

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