Effects of the synthetic ether phospholipid KO-286011 on cells and components of rabbit blood.
The ether phospholipid KO-286011, which is related to platelet-activating factor (PAF), was examined for PAF-antagonistic action on rabbit platelets both in vitro and ex vivo. It inhibited the aggregation of washed platelets induced by PAF (5 nmol/l) concentration dependently (IC50 = 6.5 X 10(-7) mol/l). After injecting 0.5 mg/kg to rabbits, the ex vivo PAF-mediated aggregation in heparinized platelet-rich plasma was influenced selectively. The inhibition was short and maximal after 5 min. In contrast, hematocrit, counts of peripheral platelets and leukocytes, hemoglobin content, partial thromboplastin time, prothrombin time, and fibrinolytic activity in plasma were not affected. However, the therapeutic range of KO-286011 is limited because of membranolytic activity at higher dosages, leading to hemolysis and drop of circulating platelet counts.
Hofmann
B
B
Institute für Pathologische Biochemie, Medizinische Akademie, Erfurt, BRD.
Greiner
J
J
Glusa
E
E
Kertscher
H P
HP
Ostermann
G
G
D000818:Animals; D001773:Blood Cells / Q000187:drug effects*; D001777:Blood Coagulation / Q000187:drug effects*; D005342:Fibrinolysis / Q000187:drug effects*; D006454:Hemoglobins / Q000378:metabolism; D010742:Phospholipid Ethers / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010976:Platelet Count / Q000187:drug effects; D011726:Pyridinium Compounds / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship
D006454:Hemoglobins; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011726:Pyridinium Compounds; C069064:KO 286011