The antithrombotic effect of KRDS, a lactotransferrin peptide, compared with RGDS.
Due to the functional homologies between milk and plasma coagulations and the molecular homologies between a plasma protein (human gamma-chain fibrinogen) and a milk protein (Kappa-casein), we thought to characterize a RGDS sequence in milk proteins. A KRDS sequence theoretically analogous to RGDS was found in human lactotransferrin. This study compares in 2 species (rat and guinea-pig) in vitro (on platelet aggregation) and in vivo (in an experimental model of arteriolar thrombosis), relative to RGDS, the effects of KRDS and of a modified sequence KRDR. In vitro, in the rat, while RGDS and KRDR did not affect significantly the platelet aggregation induced by ADP, KRDS had a significant inhibitory effect; on the guinea-pig platelets, KRDS and RGDS had an inhibitory effect of similar magnitude, and KRDR, a minimal effect. In vivo and in the two species, KRDS and RGDS had an antithrombotic activity much more pronounced than KRDR. Additionally, when KRDS and RGDS were studied together in vitro, no more than additive effect could be noticed in the guinea-pig. But in vivo, in the guinea-pig and even more pronounced in the rat, a potentiating activity was evidenced. These results indicate that KRDS, a peptide present in the human lactotransferrin sequence, has, in vitro, an anti-platelet activity and, in vivo, an anti-thrombotic activity. The mechanism of action is probably different from that of RGDS and is specific of the sequence since a similar KRDR sequence loses most of these actions.
Drouet
L
L
IVS, Hôpital Lariboisière, Paris, France.
Bal dit Sollier
C
C
Cisse
M
M
Pignaud
G
G
Mazoyer
E
E
Fiat
A M
AM
Jolles
P
P
Caen
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D005343:Fibrinolytic Agents; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007781:Lactoferrin / Q000032:analysis* / Q000494:pharmacology*; D007782:Lactoglobulins / Q000032:analysis* / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors; D051381:Rats
D005343:Fibrinolytic Agents; D007782:Lactoglobulins; D009842:Oligopeptides; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; C056549:KRDS peptide; C046617:arginyl-glycyl-aspartyl-serine; D007781:Lactoferrin