Omega-hydroxylation of prostaglandin E1 in the isolated perfused lungs of pregnant rabbits

Abstract Cytochrome P450 PGω 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 E 1 (PGE 1 ), to the lung vasculature. Isolated, perfused lungs from three pregnant and four nonpregnatn rabbits were injected with [ 3 H]-PGE 1 . One-second fractions were collected from the perfusion effluent and were analyzed for metabolism of PGE 1 . Lungs isolated from pregnant rabbits metabolized PGE 1 mainly to two polar derivatives, 20-hydroxy-PGE 1 and 13,14-dihydro-15-keto-20-hydroxy-PGE 1 , whereas lungs from nonpregnant rabbits yielded mainly a relatively nonpolar metabolite, 13,14-dihydro-15-keto-PGE 1 . 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).