PGA1 and PGF2 alpha metabolism by pig pulmonary endothelium, smooth muscle, and fibroblasts.

To determine the cellular site for uptake and degradation of circulating prostaglandins (PGs) by the lung, the metabolism of PGA1 and PGF2 alpha was studied in pig lung slices, smooth muscle preparations, and pulmonary valves, as well as in isolated and cultured endothelial cells and cultured fibroblasts. Formation of 15-keto metabolites of both PGA1 and PGF2 alpha by lung slices was confirmed. No evidence of PGF2 alpha degradation could be found in any of the remaining preparations. For PGA1, however, 15-hydroxyprostaglandin dehydrogenase activity was detected in the three smooth muscle preparations studied (trachea, aorta, pulmonary artery) and found to be similar to that measured in lung slices. But the inhibitory effect of diphloretin phosphate and bromcresol green was much more marked in smooth muscle tissues than in lung slices, which suggested that PGA1 metabolism by the lung was not due to smooth muscle cells. Endothelial cells, freshly isolated and cultured, originating from the pulmonary artery and from the aorta, formed a PGA1-glutathione adduct, poorly extractable in ethyl acetate. This reaction, also present in cultured fibroblasts, was inhibited by ethacrynic acid. The cellular site responsible for the pulmonary degradation of circulating PGs remains undetermined.