Uptake and metabolism of prostaglandins by isolated perfused lung: Species comparison and the role of plasma protein binding

We have investigated the uptake and subsequent metabolism of the prostaglandins (PGs) PGE₁, PGA₁, and PGB₁ by rat, guinea pig and rabbit isolated perfused lungs (IPL). Significant species differences were not observed in the uptake or metabolism of any PG on passage through the IPL. However, differences in the uptake of PGA₁ and PGB₁ and in the metabolism of PGA₁ were observed with a given species when the composition of the perfusion medium was varied. The IPL removed minimal amounts (<20% of the supply rate) of PGA₁ and PGB₁ from the circulation when the perfusate contained 4.5% bovine serum albumin (BSA). In the absence of BSA, however, both PGA₁ and PGB₁ were substantially removed from circulation (～53% of the supply rate) and PGA₁ was also metabolized. The composition of the perfusate had no effect on the uptake and metabolism of PGE₁ which was always taken up and metabolized to a greater extent than was PGA₁ and PGB₁. Thus, the apparent species differences previously reported for the pulmonary biotransformation of PGA can result from differences in the perfusion medium used. Our data suggest that both plasma protein binding and a transport system play important roles in determining the selectivity of the uptake of PGs by the lung.