Drouet L, Bal dit Sollier C, Cisse M, Pignaud G, Mazoyer E, Fiat A M, Jolles P, Caen J P
IVS, Hôpital Lariboisière, Paris, France.
Nouv Rev Fr Hematol (1978). 1990;32(1):59-62.
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.
由于乳凝块和血浆凝块之间存在功能同源性，且一种血浆蛋白（人γ链纤维蛋白原）和一种乳蛋白（κ-酪蛋白）之间存在分子同源性，我们认为有必要对乳蛋白中的RGDS序列进行表征。在人乳铁蛋白中发现了理论上与RGDS类似的KRDS序列。本研究比较了在两种物种（大鼠和豚鼠）中，相对于RGDS，KRDS和修饰序列KRDR在体外（对血小板聚集）和体内（在小动脉血栓形成的实验模型中）的作用。在体外，在大鼠中，虽然RGDS和KRDR对ADP诱导的血小板聚集没有显著影响，但KRDS具有显著的抑制作用；在豚鼠血小板上，KRDS和RGDS具有相似程度的抑制作用，而KRDR的作用最小。在体内和这两种物种中，KRDS和RGDS的抗血栓活性比KRDR更明显。此外，当在体外同时研究KRDS和RGDS时，在豚鼠中只能观察到相加效应。但在体内，在豚鼠中，甚至在大鼠中更明显，有增强活性的证据。这些结果表明，人乳铁蛋白序列中存在的肽KRDS在体外具有抗血小板活性，在体内具有抗血栓活性。其作用机制可能与RGDS不同，并且是序列特异性的，因为类似的KRDR序列失去了大部分这些作用。
