TY - JOUR
T1 - Omega-hydroxylation of prostaglandin E1 in the isolated perfused lungs of pregnant rabbits
AU - Leithauser, Marie T.
AU - Roerig, David L.
AU - Winquist, Sharon M.
AU - Gee, Arnold
AU - Okita, Richard T.
AU - Su Siler Masters, Bettie
N1 - Funding Information:
We would like to dedicate this publication to Dr. Elizabeth C. Miller of the McArdle Laboratory for Cancer Research. Betty's life was an inspiration to many scientists and especially to those of us who were trained by her and her husband, Dr. James A. Miller. Science has suffered a great loss with her death. This study was supported by Grant GM 31296 to B.S.S.M. and R.T.O. from the National Institutes of Health. We would like to thank Dr. Robert C. Murphy and Dr. Joseph A. Zirrolli (University of Colorado Health Sciences Center) for performing the gas chromatographic/mass spectrometric analyses (supported by NIH Grant RR01152) and for their helpful suggestions. We would also like to thank Dr. Christopher A. Dawson for his assistance and many valuable recommendations.
PY - 1988/12
Y1 - 1988/12
N2 - Cytochrome P450PGω is induced in the rabbit lung in a gestational age-dependent manner and hydroxylates certain eicosanoids at their terminal, or omega (ω), carbon. This enzyme has beenisolated from microsomal fractions and its activity has been characterized (Williams, D.E., et al., J. Biol. Chem. 259; 14600-14608, 1984). The experiments presented here examine the ω-hydroxylation activity of the intact lung during presentation of an eicosanoid substrate, prostaglandin E1 (PGE1), to the lung vasculature. Isolated, perfused lungs from three pregnant and four nonpregnatn rabbits were injected with [3H]-PGE1. One-second fractions were collected from the perfusion effluent and were analyzed for metabolism of PGE1. Lungs isolated from pregnant rabbits metabolized PGE1 mainly to two polar derivatives, 20-hydroxy-PGE1 and 13,14-dihydro-15-keto-20-hydroxy-PGE1, whereas lungs from nonpregnant rabbits yielded mainly a relatively nonpolar metabolite, 13,14-dihydro-15-keto-PGE1. These metabolites were identified by coelution with standards that were generated enzymatically in vitro and whose structures were confirmed by gas chromatography/mass spectrometry (GC/MS).
AB - Cytochrome P450PGω is induced in the rabbit lung in a gestational age-dependent manner and hydroxylates certain eicosanoids at their terminal, or omega (ω), carbon. This enzyme has beenisolated from microsomal fractions and its activity has been characterized (Williams, D.E., et al., J. Biol. Chem. 259; 14600-14608, 1984). The experiments presented here examine the ω-hydroxylation activity of the intact lung during presentation of an eicosanoid substrate, prostaglandin E1 (PGE1), to the lung vasculature. Isolated, perfused lungs from three pregnant and four nonpregnatn rabbits were injected with [3H]-PGE1. One-second fractions were collected from the perfusion effluent and were analyzed for metabolism of PGE1. Lungs isolated from pregnant rabbits metabolized PGE1 mainly to two polar derivatives, 20-hydroxy-PGE1 and 13,14-dihydro-15-keto-20-hydroxy-PGE1, whereas lungs from nonpregnant rabbits yielded mainly a relatively nonpolar metabolite, 13,14-dihydro-15-keto-PGE1. These metabolites were identified by coelution with standards that were generated enzymatically in vitro and whose structures were confirmed by gas chromatography/mass spectrometry (GC/MS).
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U2 - 10.1016/0090-6980(88)90059-7
DO - 10.1016/0090-6980(88)90059-7
M3 - Article
C2 - 3244833
AN - SCOPUS:0024265017
SN - 0090-6980
VL - 36
SP - 819
EP - 833
JO - Prostaglandins
JF - Prostaglandins
IS - 6
ER -