The Influence of Environmental Agents on Prostaglandin Biosynthesis and Metabolism in the Lung INHIBITION OF LUNG 15-HYDROXYPROSTAGLANDIN DEHYDROGENASE BY EXPOSURE OF GUINEA PIGS TO 100 PER CENT OXYGEN AT ATMOSPHERIC

Enzymes in the 100000g supematant fraction of guinea-pig lungs, in the presence of NAD+, converted PGF2a (prostaglandin F2z) into a less-polar compound. The u.v. spectrum of this metabolite showed a strong absorption band at 230nm, which is characteristic ofa carbonyl group in conjugation with a double bond. Reduction ofthis metabolite with NaBH4 resulted in a compound that behaved like PGF2. on t.l.c. and g.l.c. From this evidence we concluded that PGF2. is metabolized in vitro to 15-oxo-PGF2. by the NAD+-dependent prostaglandin dehydrogenase system of guinea-pig lung. The effect of exposure of the animal to SO2 and 02 on the rate of prostaglandin biosynthesis and catabolism by lung fractions in vitro was studied. Exposure of guinea pigs to 500p.p.m. of SO2 for 5h or to 50p.p.m. for 9 days (6h/day) did not alter the production or degradation of prostaglandins by lung fractions in vitro. In contrast, exposure of guinea pigs to 100% 02 for 48h inhibited the rate of prostaglandin metabolism in vitro by 60-70% without significantly altering the rate of biosynthesis by lung fractions. Inhibition ofprostaglandin dehydrogenase activity in vitro by lung fractions after exposure of the animal to 02 was dependent on the duration of exposure. Glutathione S-aryltransferase and catechol 0methyltransferase activities of guinea-pig lung 1000OOg supernatant were unaltered by exposure ofthe animal to 02. Thus it appears that inhibition ofpulmonary prostaglandin dehydrogenase by exposure ofthe animal to 02 is not the result ofa general toxic response. It was postulated that the inhibition of prostaglandin dehydrogenase may occur after exposure of the animal to other oxidant gases.