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

Citation
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
Citations number
25
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00909556
Volume
23
Issue
1
Year of publication
1995
Pages
83 - 89
Database
ISI
SICI code
0090-9556(1995)23:1<83:X-AMSF>2.0.ZU;2-L
Abstract
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.