Metabolism of arachidonic acid and its endoperoxide (PGH2) to myotropic products in guinea-pig and rabbit isolated lungs.
1 Conversion of arachidonic acid (AA) and its endoperoxide (PGH(2)) to myotropic metabolites has been studied in isolated Krebs-perfused lungs of guinea-pig and rabbit. A continuous differential bioassay technique was used to measure myotropic metabolites in the lung perfusate.2 AA was metabolized in guinea-pig lungs to thromboxane A(2) (TxA(2)), prostacyclin (PGI(2)) and small amounts of a prostaglandin E(2) (PGE(2))-like substance. The amounts of products were dose-related over the AA range used (1 to 10 mug). PGH(2) was detected only after AA (10 mug).3 Rabbit lungs converted AA (2.5 to 10 mug) to the same products in similar relative proportions but the amounts were 15 to 25% of those produced by guinea-pig lungs.4 Indomethacin (10 nM) preferentially inhibited metabolism of AA to prostaglandins in guinea-pig lungs but preferentially inhibited metabolism to TxA(2) in rabbit lungs. Higher concentrations (50 nM) greatly reduced conversion to all the myotropic metabolites in lungs from both species.5 Imidazole (50 muM) selectively inhibited conversion of AA to TxA(2) and increased conversion to PGI(2) in rabbit lungs. A similar effect was produced in guinea-pig lungs but with much higher concentrations of imidazole (2.5 to 5 mM).6 PGH(2) (800 ng) was converted in guinea-pig lung to TxA(2) (100 ng) and very small amounts of PGI(2) (10 to 16 ng) but only unchanged PGH(2) and some PGE(2) were present in the lung perfusate after injection of PGH(2) in rabbit lung.7 It is concluded that guinea-pig and rabbit lung differ in their ability to metabolize AA to myotropic substances and also in their response and sensitivity to drugs which interfere with prostaglandin and TxA(2) synthesis. The lungs do not appear to have an important role in converting PGH(2) to PGI(2).
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001711:Biotransformation; D001794:Blood Pressure / Q000187:drug effects; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000378:metabolism*; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D011449:Prostaglandin Endoperoxides / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D011463:Prostaglandins H / Q000378:metabolism*; D011817:Rabbits; D013928:Thromboxane A2 / Q000378:metabolism
D001095:Arachidonic Acids; D007093:Imidazoles; D011449:Prostaglandin Endoperoxides; D011453:Prostaglandins; D011463:Prostaglandins H; D013928:Thromboxane A2; D007213:Indomethacin