Leukotrienes potentiate the effects of epinephrine and thrombin on human platelet aggregation.
A cooperation between leukocytes and platelets relative to metabolism of arachidonic acid has been observed in animal studies. To determine potential stimulatory effects of leukotrienes (LTs) on human platelets, LTs were incubated with platelet rich plasma followed by addition of subthreshold concentration of aggregatory stimulus. LTs (LTE4 LTD4 LTC4) alone had no direct effect on platelet aggregation, but potentiated the effects of subthreshold concentrations of epinephrine and thrombin and caused complete platelet aggregation. This potentiation was similar in citrated or heparinized blood and was unaffected by exogenous CaCl2. LTs did not induce secondary wave of aggregation in aspirin or selective TXA2-synthetase blocker OKY-046-treated platelets. In addition, LTs stimulated TXA2 biosynthesis by platelets in the presence of subaggregatory concentrations of epinephrine, but not when platelets had been pretreated with OKY-046. These data indicate that LTs potentiate epinephrine-induced platelet aggregation by modulating TXA2 synthetase activity.
D001241:Aspirin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D017999:Leukotriene E4; D008689:Methacrylates / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D013189:SRS-A / Q000031:analogs & derivatives / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000096:biosynthesis; D013997:Time Factors
D008689:Methacrylates; D013189:SRS-A; D013928:Thromboxane A2; D017999:Leukotriene E4; D013917:Thrombin; C034364:ozagrel; D001241:Aspirin; D002118:Calcium; D004837:Epinephrine