13-cis-retinoic acid stimulates in vitro mannose 6-phosphate hydrolysis and inhibits retinol esterification and benzo[a]pyrene hydroxylation by rat-liver microsomes.
13-cis-Retinoic acid, a drug used at high doses in the treatment of recalcitrant acne, increased the permeability of rat-liver microsomal membranes to mannose 6-phosphate in vitro, as indicated by an increase in mannose-6-phosphatase activity. At the same concentrations, four other amphiphiles, including all-trans-retinoic acid, were much less effective. 13-cis-Retinoic acid also inhibited retinol esterification and benzo[a]pyrene hydroxylation in microsome preparations in vitro. Although the molecular mechanism and the reversibility of these effects have not yet been studied, the interaction of 13-cis-retinoic acid with cell membranes may well be involved in both its therapeutic and toxic manifestations.
Ball
M D
MD
Department of Biochemistry and Biophysics, Iowa State University, Ames 50011.
Olson
J A
JA
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D005260:Female; D006600:Hexosephosphates / Q000378:metabolism*; D006868:Hydrolysis; D006900:Hydroxylation; D007536:Isomerism; D015474:Isotretinoin; D007700:Kinetics; D008360:Mannosephosphates / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D014212:Tretinoin / Q000494:pharmacology*; D014801:Vitamin A / Q000378:metabolism*
D006600:Hexosephosphates; D008360:Mannosephosphates; D014801:Vitamin A; D001564:Benzo(a)pyrene; C027693:mannose-6-phosphate; D014212:Tretinoin; D015474:Isotretinoin