Platelet aggregation induced by platelet-activating factor is suppressed by cystine protease inhibitor.
The effect of NCO-700, a cystine protease inhibitor, on platelet-activating factor-induced platelet aggregation was determined. A newly synthesized cystine protease inhibitor (calcium-activated neutral protease and cathepsin B inhibitor), NCO-700 (bis[ethyl (2R, 3R)-3-[(S)-methyl-1-[4-(2,3,4- trimethoxyphenylmethyl) piperazine-1-ylcarbonyl]butylcarbonyl]oxiran-2-carboxy late]sulfate), inhibited platelet-activating factor-induced platelet aggregation. The inhibition was dependent on the preincubation time with NCO-700 and on the concentration of the inhibitor. The release of serotonin was also inhibited almost completely by the 20-min preincubation with 10(-4) M NCO-700. Leupeptin also inhibited platelet-activating factor-induced platelet aggregation. But calcium-activated neutral protease inhibitor did not inhibit it. These observations suggest that NCO-700-sensitive protease(s) such as cystine protease may contribute to platelet aggregation induced by platelet-activating factor.
Takano
H
H
Department of Cardiovascular Medicine, Hokkaido University, School of Medicine, Sapporo, Japan.
Kawaguchi
H
H
Iizuka
K
K
Yasuda
H
H
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002154:Calpain / Q000037:antagonists & inhibitors; D002401:Cathepsin B / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism
D010879:Piperazines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011480:Protease Inhibitors; D012701:Serotonin; C036798:NCO 700; D002154:Calpain; D002401:Cathepsin B; D007213:Indomethacin