XENOPUS-LAEVIS - A MODEL SYSTEM FOR THE STUDY OF EMBRYONIC RETINOID METABOLISM .2. EMBRYONIC METABOLISM OF ALL-TRANS-3,4-DIDEHYDRORETINOL TO ALL-TRANS-3,4-DIDEHYDRORETINOIC ACID
Jc. Kraft et al., XENOPUS-LAEVIS - A MODEL SYSTEM FOR THE STUDY OF EMBRYONIC RETINOID METABOLISM .2. EMBRYONIC METABOLISM OF ALL-TRANS-3,4-DIDEHYDRORETINOL TO ALL-TRANS-3,4-DIDEHYDRORETINOIC ACID, Drug metabolism and disposition, 23(1), 1995, pp. 83-89
This study demonstrates early embryonic metabolism of exogenous all-tr
ans-3,4-didehydroretinol (vitamin A(2)) to all-trans-3,4-didehydroreti
nal and to all-trans-3,4-didehydroretinoic acid in Xenopus embryos dur
ing neurulation. The latter metabolite was recently shown to bind with
high affinity and to activate various retinoic acid receptors. Embryo
s treated with all-trans-3,4-didehydroretinol during early or late gas
trulation exhibited abnormalities along the anteroposterior axis. The
abnormalities were primarily in the posterior regions of the embryo, w
ith only minor defects anteriorally. Eye malformations, typical for ea
rly exposure to 9-cis- and all-trans-retinols and retinals (companion
paper), were not observed. We also present evidence that all-trans-3,4
-didehydroretinoic acid is present endogenously during early neurulati
on and is evenly distributed along the anteroposterior axis. After tre
atment with all-trans-3,4-didehydroretinol, embryonic levels of all-tr
ans-3,4-didehydroretinoic acid exceeded endogenous levels of this meta
bolite during early and late neurulation. We hypothesize that the dysm
orphogenic effects produced by treatment of Xenopus embryos with the a
lcohol precursor, all-trans-3,4-didehydroretinol, are the result of it
s embryonic conversion to its corresponding acid ligand.