The metabolism of prostaglandin E2 is decreased by sulfinpyrazone in isolated hamster lungs

Abstract

The metabolism of prostaglandin E₂ (PGE₂) was decreased in isolated male hamster lungs, when sulfinpyrazone was infused into the pulmonary circulation. After pulmonary injection of 20 nmol of¹⁴C-PGE₂ the amount of 15-keto-metabolites of PGE₂ was in the effluent from control lungs 4.0 ± 0.5 nmol (mean ± SEM) and in those from 20 μM and 100 μM sulfinpyrazone treated lungs 1.9 ± 0.2 nmol (2P<0.01 compared to the control) and 1.7 ± 0.4 nmol (2P <0.01), respectively.The amount of unmetabolized PGE₂ was correspondingly increased in the effluent by sulfinpyrazone. The rate of efflux of the radioactivity from the lungs was increased by sulfinpyrazone. After injection of 10 nmol of ¹⁴C-PGE₂ into the pulmonary circulation half of the injected radioactivity appeared in the effluent in 30 ± 4 sec in control and in 15 ± 0.7 sec (2P <0·01) in 20 μM sulfinpyrazone experiments. Sulfinpyrazone had no effect on the activity of 15-hydroxyprostaglandin dehydrogenase in the 100.000 g supernatant fraction of homogenized hamster lungs. Thus the decreased metabolism of PGE in the pulmonary circulation of hamster lungs is obviously not due to the inhibition of 15-hydroxyprostaglandin dehydrogenase. A more likely explanation seems to be the decreased uptake of PGE₂ into the lung cells.