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

Abstract

1 Two potent inhibitors ofprostaglandin 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 I1M) and CK 61A (0.5 and 5 FM) markedly increased the survival ofprostaglandin E2 (PGE2) and PGF2, on a single passage through the pulmonary circulation.3 Both inhibitors delayed the efflux of 14C following injection of ["CJ-PGE2 through the pulmonary circulation.4 Output ofPGE2 and PGF2. but not that of6-oxo-PGF,, from exogenous arachidonic acid (AA) was increased by CL 28A. 5Output 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-PGF,, 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 ofbiologically 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.

Effect of Captopril on the bradykinin‐induced release of prostacyclin from guinea‐pig lungs and bovine aortic endothelial cells

“…They are also in agreement with the results of Mullane & Moncada (1980) who showed that captopril potentiated the release of PGI2 by Bk in dogs. The possibility that captopril enhances eicosanoid output by inhibition of prostaglandin dehydrogenase (Bakhle & Pankhania, 1987) is unlikely since it did not alter eicosanoid release after AA.…”

Modification by steroids of pulmonary oedema and prostaglandin E2 pharmacokinetics induced by endotoxin in rats

“…Rats were anaesthetized as before, the chest opened and the pulmonary artery cannulated and perfused with warmed (370C) and gassed (95% 02 + 5% C02) Krebs solution at a constant rate of 8 ml min-' as described previously (Bakhle et al, 1969 (Watts et al, 1982) and antisera (Bakhle & Pankhania, 1987) described previously. The lower limit of detection for PGE2 was 80pgml-1 and cross-reactivities were: PGE1 26%, PGF2a The total white blood cell count showed an earlier response to endotoxin (Table 1), falling to about 50% by 2h with a minimum value of just over 30% at 4 h. The total white blood cell count returned to normal by 28 h. The numbers of PMNs were also severely reduced (less than 25% of normal at 4 h) and remained low until 28 h. The proportion of PMNs in the total white blood cells also fell after endotoxin, from about 22% in untreated rats to 15% at 4 h, showing the relatively greater effect on these leukocytes.…”