In-vitro metabolism of retinoic acid by different tissues from male rats

Significant differences between the metabolism of retinoic acid by different tissues might be an important determinant of the effectiveness of a systemically administered inhibitor at a particular tissue site. Here the metabolism of retinoic acid has been studied in microsomal fractions from different tissues (liver, kidney, intestinal mucosa, lung, skin, brain) of the male rat to determine their relative metabolic activity. Kinetic analysis revealed major differences between the activity of different tissue microsomes. This is shown by the V-max values for the metabolism of retinoic acid-liver (102 +/- 39.0 pmol (mg protein)(-1)min(-1)) was 100 times more active than the lung (1 +/- 0.03 pmol (mg protein)(-1) min(-1)), which was the least active. The range of K-m values for microsomes from the different tissues was narrow (0.48-1.40 mu M). Taking into account the mass of the tissue, the gross activity ranking for metabolism of retinoic acid was liver>>skin = kidney > brain > intestinal mucosa>>lung. It is concluded that metabolism of administered retinoic acid occurs mainly in the liver but that cellular retinoic acid levels in some other tissues (skin, kidney, brain) could be reduced (metabolized) to such an extent that higher levels might be observed after the use of inhibitors of retinoic acid metabolism.