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 pressure

Abstract

Enzymes in the 100 000g supernatant fraction of guinea-pig lungs, in the presence of NAD-+, converted PGF-2 alpha (prostaglanding F-2 alpha) into a less-polar compound. The u.v. spectrum of this metabolite showed a strong absorption band at 230 nm, which is characteristic of a carbonyl group in conjugation with a double bond. Reduction of this metabolite with NaBH4 resulted in a compound that behaved like PGF2 ALPHA on t.l.c. and g.l.c. From this evidence we concluded that PGF2alpha is metabolized in vitro to 15-oxo-PGF2 alpha by the NAD-+-dependent prostaglandin dehydrogenase system of guinea-pig lung. The effect of exposure of the animal to SO-2 and O2 on the rate of prostaglanding biosynthesis and catabolism by lung fractions in vitro was studied. Exposure of guinea pigs to 500 p.m. of SO2 for 5h or to 50p.p.m for 9 days (6h/day) did not alter the production or degradation of prostaglandings by lung fractions in vitro. In contrast, exposure of guinea pigs to 100% O2 for 48 h inhibited the rate of prostaglanding metabolism in vitro by 60-70% without significantly altering the rate of biosynthesis by lung fractions. Inhibition of prostaglandin dehydrogenase activity in vitro by lung fractions after exposure of the animal to O2 was dependent on the duration of exposure. Gluthathione S-aryltransferase and catechol O-methyltransferase activites of guinea-pig lung 100 000g supernatant were unaltered by exposure of the animal to O2. Thus it appears that inhibition of pulmonary prostaglandin dehydrogenase by exposure of the animal to O2 is not the result of a general toxic response. It was postulated that the inhibition of prostaglanding dehydrogenase may occur after exposure of the animal to other oxidant gases.

Inhibition of pulmonary prostaglandin metabolism by exposure of animals to oxygen or nitrogen dioxide

“…1. Prostaglandin dehydrofrom three genase activity, expressed as a percentage of the conf metabolite trol value, decreased linearly with time of exposure to 100%O 02, which in agreement with our previous reported data (Parkes & Eling, 1975). After the exposure to 100% 02 was stopped, prostaglandin I animals was dehydrogenase activity in lung increased with time hat found in until control values were reached in 7 days (Fig.…”

“…We examined the effect of animal exposure to 02 on the activities of other pulmonary enzyme systems. The enzymic activities of catechol O-methyltransferase, glucose 6-phosphate dehydrogenase and glutathione S-aryltransferase (Parkes & Eling, 1975), enzymes found in the lOOOOOg supernatant fraction and microsomal prostaglandin synthetase were not inhibited by 02 exposure. Thus 02 exposure does not produce a general inhibition of soluble enzymes.…”

“…For exposure to 02, animals were placed in airtight polystyrene cages as described previously (Parkes & Eling, 1975). The O2 concentration was verified by measurement of PO2 with a blood-gas analyser.…”

“…Incubations were carried out for 15min at 37°C in a Dubnoff metabolic shaker. The metabolite, 15-oxoprostaglandin F2a was separated and determined by the method described by Parkes & Eling (1975). Kinetic-analysis assay procedure.…”

“…Tubes containing less than 40pM-NAD+ were incubated for 20min, whereas those of 40,M-NAD+ or higher were incubated for 10min. The metabolite, 15-oxoprostaglandin F2,, was separated and determined by the method described by Parkes & Eling (1975).…”