Release of tissue-type plasminogen activator is induced in rats by leukotrienes C4 and D4, but not by prostaglandins E1, E2 and I2.

1. Acute release of plasminogen activator (PA) was studied in rat isolated hindleg system perfused with Tyrode solution. 2. Leukotriene C4 (LTC4) and LTD4 dose-dependently induced the release of PA, which plateaued at 160 nmol l-1 and 200 nmol l-1, respectively. The amount of PA released was about 1 iu ml-1. The effects of LTC4 and LTD4 were not additive. 3. The PA released was identified as tissue-type PA (t-PA) by quenching experiments using anti-human t-PA IgG, by fibrin autography, and by the dependence of its activity on the presence of soluble fibrin. 4. LTE4 (300 and 450 nmol l-1) and 5-hydroxy-eicosatetraenoic acid (600 nmol l-1) did not induce any t-PA release in the perfusion system used. 5. Release of t-PA induced by LTC4 and LTD4 was inhibited by the leukotriene-receptor antagonist FPL 55712 (10 mumol l-1), whereas FPL 55712 did not inhibit t-PA release induced by platelet-activating factor (Paf-acether). 6. In vivo LTC4 and LTD4 (2 micrograms kg-1 i.v.) also induced an acute increase of t-PA activity in rat blood as evidenced by decreased blood clot lysis times. 7. Prostaglandin E1 and E2, prostacyclin and the stable prostacyclin analogue ZK 36374 at concentrations of 0.1-3.0 mumol l-1 induced little or no t-PA release.