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

Significant differences between the metabolism of retinoic acid by differen t tissues might be an important determinant of the effectiveness of a syste mically administered inhibitor at a particular tissue site. Here the metabo lism of retinoic acid has been studied in microsomal fractions from differe nt tissues (liver, kidney, intestinal mucosa, lung, skin, brain) of the mal e rat to determine their relative metabolic activity. Kinetic analysis revealed major differences between the activity of differe nt 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 th e different tissues was narrow (0.48-1.40 mu M). Taking into account the ma ss of the tissue, the gross activity ranking for metabolism of retinoic aci d 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 ac id metabolism.