Rabbit lung microsomes: a rapid method for assaying simultaneously drug effects on thromboxane and prostacyclin synthesis.
A radiochemical method is described which allows simultaneous determination of the in vitro effects of chemical substances on thromboxane and prostacyclin synthesis. The method utilizes the capacity of a combination of bovine seminal vesicle microsomes (BSVM) and rabbit lung microsomes (TbLM) to transform arachidonic acid into TXB2, 12-hydroxy-heptadecatrienoic acid (HHT), 6-keto-PGF1 alpha (6K-PGF1 alpha), PGF2 alpha, and PGE2 in the ratio of 1:0.80:0.63:0.13:0.05, respectively. Imidazole and burimamide, and to some degree also dipyridamole and L8027, were found to be selective thromboxane inhibitors. The preferential alternative pathways following thromboxane inhibition with these drugs were towards PGE2 and PGF2 alpha, and the algebraic sum of arachidonic acid metabolism was not affected by imidazole and burimamide. The assay is a convenient method for identification of drugs which interfere with specific pathways of arachidonic acid metabolism.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D002049:Burimamide / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis*; D006830:Hydralazine / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D011817:Rabbits; D013931:Thromboxanes / Q000096:biosynthesis*
D001095:Arachidonic Acids; D007093:Imidazoles; D011453:Prostaglandins; D013931:Thromboxanes; D006830:Hydralazine; D004176:Dipyridamole; D011464:Epoprostenol; D001241:Aspirin; D002049:Burimamide; D007213:Indomethacin