Control of prostanoid synthesis: role of reincorporation of released precursor fatty acids.
Prostanoid synthesis is limited by the availability of free arachidonic acid. This polyunsaturated fatty acid is liberated by phospholipases and usually is an intermediate of the deacylation-reacylation cycle of membrane phospholipids. In rat peritoneal macrophages, ethylmercurisalicylate (merthiolate) or N-ethylmaleimide (NEM) dose dependently inhibited the incorporation of arachidonic acid into cellular phospholipids, at lower concentrations specifically into phosphatidylcholine. Furthermore, merthiolate could be shown to be a rather selective inhibitor of lysophosphatidylcholine acyltransferase. In contrast, phospholipase A2 activity was not affected over a wide dose range. Consequently, macrophages showed a large increase in prostanoid synthesis (prostaglandin E, prostacyclin and thromboxane) in the presence of both lysophosphatide acyltransferase inhibiting agents. Similar results were obtained with human platelets, in which merthiolate increased the release of thromboxane. Addition of free arachidonic acid also enhanced prostanoid synthesis in macrophages. At optimal concentrations, merthiolate had no further augmenting effect. It is concluded that the rate of prostanoid synthesis is not only controlled by phospholipase A2 activity, but rather by the activity of the reacylating enzymes, mainly lysophosphatide acyltransferase.
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D010537:Peritoneum / Q000166:cytology; D010743:Phospholipids / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011917:Rats, Inbred Lew; D013849:Thimerosal / Q000494:pharmacology; D013931:Thromboxanes / Q000096:biosynthesis; D015054:Zymosan / Q000494:pharmacology
D005227:Fatty Acids; D010743:Phospholipids; D011453:Prostaglandins; D013931:Thromboxanes; D013849:Thimerosal; D003094:Collagen; D015054:Zymosan; D005033:Ethylmaleimide