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.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001391:Azo Compounds / Q000494:pharmacology*; D006911:Hydroxyprostaglandin Dehydrogenases / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010648:Phenylacetates / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D001391:Azo Compounds; D010648:Phenylacetates; D011453:Prostaglandins; D016718:Arachidonic Acid; C054081:5-(4-carboxyphenyl)azo-2-hydroxybenzeneacetic acid; C047498:Ph CL 28A; D006911:Hydroxyprostaglandin Dehydrogenases