Studies on the mode of action of excess of vitamin A. 4. The specificity of the effect on embryonic chick-limb cartilage in culture and on isolated rat-liver lysosomes

Abstract

A number of compounds, including derivatives of vitamin A, terpenes and alcohols, have been examined for ability to reproduce the effects of vitamin A on embryonic chick-limb cartilage in culture and on the release of cathepsin from isolated lysosomes. In the organ cultures at a concentration of 0.01 [mu]mole/ml none of the compounds examined, except vitamin A acid, had a significant effect on the explants; the effects of this derivative were indistinguishable from those produced by vitamin A. At a concentration of 0.1 [mu]mole/ml hydrogenated vitamin A and [beta]-ionone slightly reduced the growth in length of the explants, but caused little histological change. Approximately 2/3 of the bound protease was released from isolated rat-liver lysosomes by 0.7 [mu]mole of vitamin A/ml. Of the compounds studied at this concentration and under the same conditions, only vitamin A acid had an effect comparable with that of the vitamin; other derivatives of vitamin A were inactive, and most of the terpenes had about 25% of the activity of the vitamin. At higher concentrations the specificity of the vitamin was reduced. The results indicate that the action of vitamin A is highly specific on cartilage in culture and also at low concentrations on the isolated lysosomes.