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Thromb Haemost 1995; 73(05): 857-861
DOI: 10.1055/s-0038-1653881
Original Articles
Platelets
Schattauer GmbH Stuttgart

KRDS, a Peptide Derived from Human Lactotransferrin, Inhibits Thrombin-Induced Thromboxane Synthesis by a Cyclooxygenase-Independent Mechanism

Sylviane Lévy-Toledano
The U INSERM 348, I.F.R. Biologie de la Circulation-Lariboisiére, Paris, France
,
Françoise Grelac
The U INSERM 348, I.F.R. Biologie de la Circulation-Lariboisiére, Paris, France
,
Jacques P Caen
*   Institut des Vaisseaux et du Sang, Hôpital Lariboisiére, Paris, France
The U INSERM 348, I.F.R. Biologie de la Circulation-Lariboisiére, Paris, France
,
Jacques Maclouf
The U INSERM 348, I.F.R. Biologie de la Circulation-Lariboisiére, Paris, France
› Author Affiliations
Further Information

Publication History

Received 22 August 1994

Accepted after resubmission 24 January 1995

Publication Date:
09 July 2018 (online)

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Summary

KRDS, a tetrapeptide from human lactotransferrin, inhibits thrombin-induced platelet aggregation, secretion and thromboxane (TX) synthesis without interfering with phospholipase C (PLC) β activation, since in previous work we have shown that Ca2+ mobilization and phosphorylation of the myosin light chain kinase (20 kDa) and pleckstrin (47 kDa) were normal. However, the inhibition of arachido- nic acid-induced aggregation in the presence of KRDS is accompanied by normal TX synthesis suggesting that it does not interfere with the cyclooxygenase activity. To elucidate further the mechanisms of action of this peptide we tested its effect on U46619-induced platelet activation. KRDS inhibits U46619-induced platelet aggregation time- and dose-dependently without inhibiting the phosphorylation of pleckstrin. This suggests that the PLC pathway is not affected and that the inhibitory effect of KRDS is not due to an uncoupling of TXA2 from its receptor. In addition to the PLC pathway, protein tyrosine kinases play a major role in platelet signal transduction mechanisms. At least 7 tyrosine-phosphorylated proteins are detected upon stimulation of platelets by thrombin. KRDS strongly inhibits the tyrosine- phosphorylated substrates, in particular two 100-105 kDa substrates which are related to GP Ilb/IIIa activation and platelet aggregation. The absence of TX synthesis observed in the presence of KRDS could be due to the inactivation of cPLA2 since the latter needs tyrosine phosphorylation to be activated, thus explaining the inhibitory action of KRDS on platelet functions.

 

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