RETINOIDS - IN-VITRO INTERACTION WITH RETINOL-BINDING PROTEIN AND INFLUENCE ON PLASMA RETINOL

Studies have been conducted to investigate the structure-function rela tionships of retinoids in their in vitro interaction with plasma retin ol-binding protein (RBP) and in their influence on plasma retinol conc entration. Two classes of retinoids, one bearing modifications in the area of the retinol hydroxyl end group (fenretinide, N-(ethyl) retinam ide, all-trans, and 13-cis retinoic acid) and the other one also beari ng modifications in the area of the cyclohexene ring (etretinate, acit retin, and arotinoid Ro 13-7410), were investigated. Whereas substanti al modifications of the retinol hydroxyl group do not prevent the bind ing to RBP, an intact trimethylcyclohexenyl group seems to be crucial for binding. Both classes of retinoids, administered orally at equimol ar doses, reduce plasma retinol concentration in rats but with differe nt kinetics. A marked lowering of plasma retinol occurs early (within 5 h) after administration of retinoids that interact with RBP in vitro , whereas it occurs at later times (24 h) after retinoids that do not interact with RBP. The concentrations of both classes of retinoids fou nd in plasma do not account for the temporal difference in this effect . The early reduction of plasma retinol might be the consequence of in vivo specific binding of retinoids to RBP, as suggested by the in vit ro results. The late reduction observed for retinoids lacking in vitro affinity for RBP is due to other mechanisms or to metabolism to retin oids binding to RBP.