Biosynthesis of prostaglandin E 2  in human skin: subcellular localization and inhibition by unsaturated fatty acids and anti-inflammatory drugs.
The biosynthesis of prostaglandin E(2) (PGE(2)) from [1-(14)C]arachidonic acid has been demonstrated in homogenates and subcellular fractions of human epidermis. This biosynthetic capacity is localized in the microsomal fraction, indicating the presence of an active prostaglandin synthetase system associated with membranes of the skin. The incorporation of (14)C from [1-(14)C]arachidonic acid into PGE(2) by the microsomal fraction was enhanced by EDTA. This apparent increase in (14)C incorporation into PGE(2) in the presence of EDTA could be due at least in part to its chelating properties of removing the divalent cations in the homogenate that enhance the selective formation of PGF(2alpha) and the suppression of the activity of epidermal phospholipase A, which causes the release of nonradioactive fatty acid precursors from endogenous phospholipids. This study has also demonstrated that the formation of PGE(2) from arachidonic acid by the microsomal fraction from human skin could be inhibited by polyunsaturated fatty acids, suggesting a possible regulatory role of fatty acids released from endogenous phospholipids on prostaglandin synthesis in this tissue. The inhibitory effects of some anti-inflammatory drugs on skin microsomal prostaglandin synthetase were also demonstrated in these studies. Results from these studies indicate that the skin is therefore a useful tissue for the study of mechanisms of prostaglandin biosynthesis and the mode of action of various anti-inflammatory drugs.
D001095:Arachidonic Acids / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D002247:Carbon Isotopes; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D003907:Dexamethasone / Q000494:pharmacology*; D004492:Edetic Acid / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D014222:Triamcinolone Acetonide / Q000494:pharmacology*
D001095:Arachidonic Acids; D002247:Carbon Isotopes; D005231:Fatty Acids, Unsaturated; D011453:Prostaglandins; D003907:Dexamethasone; D004492:Edetic Acid; D014222:Triamcinolone Acetonide; D001241:Aspirin; D007213:Indomethacin