Inhibitors of prostaglandin dehydrogenase (Ph CL 28A and Ph CK 61A) increase output of prostaglandins from rat isolated lung.

1 Two potent inhibitors of prostaglandin dehydrogenase (PGDH), Ph CL 28A and Ph CK 61A, have been investigated for their effects on prostaglandin catabolism and synthesis in rat isolated lung. 2 Both CL 28A (0.3 microM) and CK 61A (0.5 and 5 microM) markedly increased the survival of prostaglandin E2 (PGE2) and PGF2 alpha on a single passage through the pulmonary circulation. 3 Both inhibitors delayed the efflux of 14C following injection of [14C]-PGE2 through the pulmonary circulation. 4 Output of PGE2 and PGF2 alpha but not that of 6-oxo-PGF1 alpha from exogenous arachidonic acid (AA) was increased by CL 28A. 5 Output of all three prostaglandins from endogenous AA stimulated by calcium ionophore A23187 was increased by CL 28A. 6 With CK 61A, output of 6-oxo-PGF1 alpha from exogenous AA was not increased but that from endogenous AA was increased by either concentration of this inhibitor. 7 We conclude that it is possible to increase output of biologically active prostaglandins from lung by preventing their inactivation in situ. 8 The apparent selectivity of PGI2 synthesis from endogenous AA to potentiation by the inhibitors may have therapeutic possibilities.