Mechanism of Steroid-Induced Inhibition of Prostaglandin Production by Rat Renomedullary Cells in Culture
The mechanism by which steroids induce the inhibition of prostaglandin biosynthesis is now rather well documented. If it is generally accepted that steroids at high doses are able to stabilize cell membranes,1,2 this stabilizing property cannot account for the steroid’s ability to interfere with prostaglandin synthesis. Several authors reported that steroids inhibit the synthesis of prostaglandins by decreasing the release of arachidonic acid from the membranous phospholipids and consequently its availability for cyclooxygenase.3–6 We7 and others8–11 have shown that the anti-inflammatory effects of steroids are mediated through receptor occupancy7 and require RNA and protein synthesis.7–11 The nature and the identification of the protein(s) involved are now under study: Blackwell et al.12 and Hirata et al.13 have described the synthesis of polypeptides induced by anti-inflammatory steroids. One of these polypeptides has been described in rat macrophages by Blackwell et al.12 The polypeptide which was named “macrocortin” has a molecular weight of 15,000 and is able to inhibit phospholipase A2 activity in intact cells. Hirata et al.13 described another polypeptide, “lipomodulin,” synthetized by rabbit polymorphonuclear neutrophils, whose molecular weight is 45,000. The debate is still continuing as to whether these peptides are similar, i.e., whether lipomodulin is the precursor of macrocortin.
KeywordsArachidonic Acid Prostaglandin Synthesis Liquid Scintillation Spectrometry Cyclooxygenase Activity Exogenous Arachidonic Acid
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