Comparative study of natural and synthetic retinoids as inhibitors of arachidonic acid release and metabolism in rat peritoneal macrophages.
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.
Fiedler-Nagy
C
C
Research Division, Hoffmann-La Roche Inc., Nutley, N.J.
Wittreich
B H
BH
Georgiadis
A
A
Hope
W C
WC
Welton
A F
AF
Coffey
J W
JW
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
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