tretinoin and dansyl-chloride

The retinoid drugs have profound effects on many aspects of skin biology. The exact activity profile depends on the particular analog and its route of administration. The topical retinoids used at present have marked therapeutic effects on epidermal cell production and desquamation. All-trans-retinoic acid (tretinoin) also acts on dermal connective tissue and microvasculature in a way that is less well established but may also be of therapeutic benefit. We investigated both tretinoin and motretinide in normal subjects and in patients with ichthyosis. The quantitative dansyl chloride test has been particularly useful in monitoring the desquamatory action of these topically applied retinoids. Both compounds resulted in enhanced rates of epidermopoiesis and desquamation. Marked changes in the cytochemical profile of the epidermis were also detected, changes that differed somewhat from the alterations induced by the systemic administration of etretinate. Changes in dermal structure and vascularization were monitored by A-scan ultrasound and laser Doppler flowmetry. However, only minor changes were recorded, probably because of the comparatively short application time. These newer techniques for investigating skin structure and function offer considerable opportunities for delineating the action of retinoids.

Topics: Administration, Topical; Clinical Trials as Topic; Dansyl Compounds; Double-Blind Method; Humans; Ichthyosis; Lasers; Random Allocation; Skin; Tretinoin; Ultrasonography

The retinol carrier retinol-binding protein (RBP) forms a complex with the thyroid hormone binding protein transthyretin in the plasma of a number of vertebrate species. The interactions of retinoid-RBP complexes, as well as of unliganded RBP, with transthyretin have been investigated by means of fluorescence anisotropy studies. The presence of two independent and equivalent RBP binding sites per transthyretin molecule has been established for proteins purified from species distant in evolution. Although the natural ligand retinol participates in the interaction between retinol-RBP and transthyretin, its binding to RBP is not a prerequisite for protein-protein interaction. The dissociation constants of human transthyretin binding liganded and unliganded forms of human RBP were determined to be: all-trans retinol-RBP, Kd approximately 0.2 microM; apoRBP, Kd approximately 1.2 microM; all-trans retinoic acid-RBP, Kd approximately 0.8 microM; all-trans retinyl methyl ether-RBP, Kd approximately 6 microM. The complex of RBP with the synthetic retinoid fenretinide, which bears the bulky hydroxyphenyl end group, exhibits negligible affinity for transthyretin. The replacement of RBP-bound retinol with synthetic retinoids affects RBP-transthyretin recognition to an extent that appears to be well correlated with the nature and steric hindrance of the groups substituting the retinol hydroxyl group, consistent with their location at the interface between the contact areas of RBP and transthyretin.

Topics: Animals; Antineoplastic Agents; Apoproteins; Chickens; Dansyl Compounds; Fenretinide; Fluorescence Polarization; Humans; Molecular Structure; Prealbumin; Protein Binding; Retinoids; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma; Thyroxine; Tretinoin; Vitamin A