Induction of prostanoid synthesis in human platelets by the late complement components C5b-9 and channel forming antibiotic nystatin: inhibition of the reacylation of liberated arachidonic acid.
Treatment of human platelets by the purified late complement components C5b-9 results in a dose- and time-dependent release of prostaglandin E (PGE) and thromboxane B2 (TXB2). To study the mechanism underlying the complement-induced prostanoid synthesis, we examined whether C5b-9 affected the enzyme acyl-coA:lysolecithin acyltransferase (E.C.2.3.1.2.3) that catalyzes the reinsertion of liberated arachidonic acid, the precursor molecule of the prostanoids. With C5b-9 doses sufficient to induce prostanoid synthesis, the activity of lysolecithin acyltransferase, measured as conversion of lysophosphatidyl choline to phosphatidyl choline, was inhibited. For comparison, another channel-forming substance, nystatin, was studied. Nystatin had an effect similar to C5b-9: PGE and TXB2 release was stimulated, whereas acyltransferase activity was inhibited. These finding support the concept that inhibition of lysolecithin acyltransferase might be the prerequisite for prostanoid production.
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D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000037:antagonists & inhibitors; D000215:Acylation; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors*; D001792:Blood Platelets / Q000378:metabolism*; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000502:physiology*; D006801:Humans; D007473:Ion Channels / Q000187:drug effects; D007700:Kinetics; D009761:Nystatin / Q000494:pharmacology*; D011458:Prostaglandins E / Q000096:biosynthesis*; D013849:Thimerosal / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
D001095:Arachidonic Acids; D015938:Complement Membrane Attack Complex; D007473:Ion Channels; D011458:Prostaglandins E; D013931:Thromboxanes; D009761:Nystatin; D013849:Thimerosal; D016718:Arachidonic Acid; D013929:Thromboxane B2; D003165:Complement System Proteins; D008243:1-Acylglycerophosphocholine O-Acyltransferase