In vitro and in vivo anti-platelet effects of enzymatic hydrolysates of collagen and collagen-related peptides.
Collagen-related peptides, Gly-Pro-Arg and its analogues, were examined for their inhibitory effects on platelet aggregation induced by the addition of ADP. Human platelet aggregation was suppressed by more than 50% with each of Gly-Pro-Arg and such Gly-Pro-Arg-containing peptides as Gly-Pro-Arg-Gly, Gly-Pro-Arg-Gly-Pro, Gly-Pro-Arg-Pro-Pro, and Gly-Pro-Arg-Pro-Pro-Pro at a concentration of 0.3 mM. The inhibitory effects of these peptides were about 10 times higher in human PRP than in rat PRP. Other Gly-Pro-Arg analogues such as Sar-Pro-Arg, Gly-Pro-Lys, Gly-Ala-Arg, and Ala-Gly-Pro-Arg had no inhibitory effect at a concentration from 0.1 to 0.8 mM even in human PRP. Intravenous and oral administrations of Gly-Pro-Arg and enzymatic hydrolysates of collagen suppressed the decrease in platelet count for endotoxin-induced DIC in rats. Collagen itself has been regarded as a potent inducer of platelet aggregation, but these findings suggest that collagen-related peptides and enzymatic hydrolysates of collagen prevent platelet aggregation.
Nonaka
I
I
Department of Health and Dietary Science, Nippon Meat Packers, Inc., Ibaraki, Japan.
Katsuda
S
S
Ohmori
T
T
Shigehisa
T
T
Nakagami
T
T
Maruyama
S
S
D000818:Animals; D003094:Collagen / Q000737:chemistry*; D017364:Collagenases; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D006868:Hydrolysis; D008070:Lipopolysaccharides; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010976:Platelet Count / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013820:Thermolysin
D008070:Lipopolysaccharides; D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors; C035024:glycyl-prolyl-arginine; D003094:Collagen; D017364:Collagenases; D013820:Thermolysin