Inhibition of complement-mediated hepatic thromboxane production by mepacrine, a phospholipase inhibitor.
Complement-mediated thromboxane production in the isolated, perfused rabbit liver has been shown to be calcium sensitive. The present study utilizes mepacrine, a phospholipase inhibitor, to investigate the involvement of phospholipases A and C in the mechanism of complement-induced arachidonate metabolism. Livers perfused in vitro in an open, nonrecirculating system were given either normal plasma or zymosan activated plasma at a rate of 1 ml/minute for 10 minutes. An additional group of livers was constantly perfused with 10 microM mepacrine while receiving the zymosan activated plasma infusion. Control group livers demonstrated a stable perfusion pressure, rate of release of lactic dehydrogenase and acid phosphatase, and stable rates of thromboxane and prostacyclin production for the entire experimental period. In contrast, treatment with zymosan-activated plasma resulted in significant increases in the rate of thromboxane B2 release at 1, 3 and 5 minutes of infusion when compared to the values of the control group. Neither prostacyclin release nor enzyme release changed significantly as a result of the zymosan-activated plasma administration. Treatment of the perfused livers with mepacrine abolished the complement-mediated production of thromboxane B2. In summary, this study has confirmed that plasma which has had its complement components activated by zymosan induces a transient, self-limiting production of thromboxane-like materials in the perfused rabbit liver. The mechanism of this stimulation is hypothetized to be a mepacrine-sensitive activation of phospholipase.
Flynn
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JT
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D011464:Epoprostenol / Q000096:biosynthesis; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008102:Liver Circulation / Q000187:drug effects; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D011796:Quinacrine / Q000494:pharmacology*; D011817:Rabbits; D013931:Thromboxanes / Q000096:biosynthesis*; D015054:Zymosan / Q000494:pharmacology
D013931:Thromboxanes; D015054:Zymosan; D011464:Epoprostenol; D007770:L-Lactate Dehydrogenase; D010740:Phospholipases; D000135:Acid Phosphatase; D011796:Quinacrine