Evaluation of retinoids as inhibitors of [3H] all-trans retinoic acid binding to cellular retinoic acid-binding protein in rat skin and testes.

These experiments were designed to test the ability of certain analogs and metabolites of all-trans-retinoic acid (RA), 13-cis-retinoic acid, 4-hydroxy-all-trans-retinoic acid, 4-keto-all-trans-retinoic acid, trimethylmethoxyphenol (TMMP) analog of retinoic acid, and TMMP analog of ethyl retinoate (etretinate) to compete for cellular retinoic acid-binding protein (CRABP) in skin and testes of rats. All retinoids, except etretinate, bind to CRABP in a competitive manner with a similar affinity (approximately 5 X 10(-9) M for skin and 3 X 10(-9) M for testes). In contrast, etretinate binds in a noncompetitive manner with a much lower affinity (7.7 X 10(-5) M for skin and 7.5 X 10(-5) M for testes). The values (microM) of IC50 for CRABP from rat skin are 0.43, 0.41, 0.95, 0.83, and 77.4 and those from rat testes are 0.59, 1.29, 2.25, 2.30, and 75.25 for all-trans-RA, 13-cis-RA, 4-hydroxy-all-trans RA, 4-keto-all-trans-RA, TMMP analog of RA, and etretinate, respectively. Etretinate is a potent retinoid that is used in the treatment of psoriasis. The lack of quantitative correlation between IC50 and the biological activity of etretinate may be explained in that the active form of etretinate in the body may be the carboxylic acid form (TMMP analog of RA) which binds to CRABP with higher affinity.