Inactivation of prostaglandins in the perfused rat lung.

Inactivation in the isolated perfused rat lung of prostaglandins (PG) D2, E1, F2 alpha, I2 and the metabolites 6-keto PGF1 alpha (=6KF1 alpha) and 13, 14-dihydro-15-keto PGF2 alpha (= KH2F2 alpha) was studied using 5 min perfusion of 7-10 ng/ml PG in Krebs' solution containing 0.02 microCi/ml tritiated PG and 4.5% bovine serum albumin (BSA). The parameters measured were (a) extent of inactivation (F2 alpha greater than E1 greater than D2 greater than 6KF1 alpha greater than I2; KH2F2 alpha unchanged), (b) the accumulation of PG within the lung measured as tissue to medium ratio (F2 alpha = D2 greater than E1 greater than 6KF1 alpha greater than I1 - KH2F2 alpha) and (c) rate of equilibration of PG within the lung measured as "wash-in t 1/2" (D2 greater than F2 alpha greater than E1 greater than I2 = 6KF1 alpha = KH2F2 alpha). Removal of sodium ions produced a small decrease in PGD2 and PGE1 breakdown but not of PGF2 alpha whereas breakdown of all PGs was markedly inhibited at 5 degrees. Removal of BSA enhanced PGE1 and PGI2 breakdown but not that of PGF2 alpha. Addition of 10% BSA inhibited PGE1 breakdown but not that of PGF2 alpha. Binding of PGs to 4.5% BSA was PGE1 = KH2F2 alpha greater than D2 greater than F2 alpha, and increased at 10% BSA or after removal of sodium ions. These data support the view that PGs must be taken up into pulmonary cells by a transmembrane carrier process as a prerequisite for enzymatic breakdown. The metabolites are then released back into the pulmonary circulation.