title: Comparative study of natural and synthetic retinoids as inhibitors of arachidonic acid release and metabolism in rat peritoneal macrophages.
abstract: The effect of several natural and synthetic retinoids on the release and metabolism of arachidonic acid (20:4) in rat peritoneal macrophages (M phi), stimulated in vitro by either Ca2+ ionophore A23187 (A23187), opsonized zymosan (OZ) or 12-O-tetradecanoylphorbol-13-acetate (TPA), was investigated. With the exception of Ro 10-1670, the retinoids containing a free carboxylic acid group [i.e., all-trans-retinoic acid (all-trans-RA), 13-cis-RA, Ro 13-7652, Ro 12-7310 and Ro 13-7410] inhibited 20:4 metabolite formation in A23187- and OZ-stimulated Mø at 1-33 microM. However, only all-trans-RA, Ro 12-7310 and Ro 13-7410 inhibited the formation of 20:4 metabolites in TPA-stimulated Mø. These data suggest that part of the therapeutic effect of retinoids in inflammatory, hyperproliferative dermatologic conditions might be attributed to reduced 20:4 metabolite production.
authors.affiliation: Research Division, Hoffmann-La Roche Inc., Nutley, N.J.
authors.forename: C
authors.initials: C
authors.lastname: Fiedler-Nagy
authors.forename: B H
authors.initials: BH
authors.lastname: Wittreich
authors.forename: A
authors.initials: A
authors.lastname: Georgiadis
authors.forename: W C
authors.initials: WC
authors.lastname: Hope
authors.forename: A F
authors.initials: AF
authors.lastname: Welton
authors.forename: J W
authors.initials: JW
authors.lastname: Coffey
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D015232:Dinoprostone; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010533:Peritoneal Lavage; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D011458:Prostaglandins E / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012176:Retinoids / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis; D015054:Zymosan / Q000494:pharmacology
chemical_list: D005231:Fatty Acids, Unsaturated; D016859:Lipoxygenase Inhibitors; D011458:Prostaglandins E; D012176:Retinoids; D007975:Leukotriene B4; D000001:Calcimycin; D013929:Thromboxane B2; D015054:Zymosan; D010741:Phospholipases A; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate