cAMP-dependent regulation of P450-catalyzed dealkylation in rat conceptal tissues.
Exposures of cultured whole rat conceptuses to varying concentrations of dibutyryl cyclic AMP or isobutylmethylxanthine, alone or in combination, resulted in significant increases in rates of cytochrome P450-dependent depentylation of pentoxyphenoxazone in cell-free preparations. Lesser increases in rates of debenzylation of benzyloxyphenoxazone were also observed. In cultured whole conceptuses, basal depentylase and debenzylase activities in the visceral yolk sac were approximately sixfold higher than in the embryo. The ectoplacental cone and decidual tissues exhibited no detectable depentylase activity. Only the visceral yolk sac exhibited increased depentylase activity in response to dibutyryl cyclic AMP and isobutylmethylxanthine. Inhibitory antibodies raised against adult hepatic P450s IIB1, IIC11, and IA1 failed to significantly inhibit the yolk sac depentylase activities of noncultured conceptuses. The results suggested that the conceptal depentylation reaction may be catalyzed by a unique P450 isoform(s) that is not expressed during adult life.
Lee
Q P
QP
Dept. of Pharmacology, School of Medicine, University of Washington, Seattle 98195.
Yang
H Y
HY
Namkung
M J
MJ
Juchau
M R
MR
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D046508:Culture Techniques; D000242:Cyclic AMP / Q000502:physiology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003640:Dealkylation; D004622:Embryo, Mammalian / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D008845:Microinjections; D010078:Oxazines / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D007527:Isoenzymes; D010078:Oxazines; C014180:resorufin; D003994:Bucladesine; D003577:Cytochrome P-450 Enzyme System; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine