Comparative Study of Natural and Synthetic Retinoids as Inhibitors of Arachidonic Acid Release and Metabolism in Rat Peritoneal Macrophages

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Abstract
The effect of several natural and synthetic retinoids on the release and metabolism of arachidonic acid (20:4) in rat peritoneal macrophages (Mø), stimulated in vitro by either Ca2+ ionophore A23187 (A23187), opsonized zymosan (OZ) or 12–0-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 μM 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.

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