Metabolism of prostaglandin endoperoxide by microsomes from cat lung.
It has been reported that the prostaglandin (PG) precursor, arachidonic acid, produces divergent hemodynamic responses in the feline pulmonary vascular bed. However, the pattern of arachidonic acid products formed in the lung of this species is unknown. In order to determine the type and activity of terminal enzymes in the lung, prostaglandin biosynthesis by microsomes from cat lung was studied using the prostaglandin endoperoxide, PGH2, as a substrate. The major products of incubations of PGH2 with microsomes were thromboxane (TX) B2 (the major metabolite of TXA2), 6-keto-PGF1 alpha (the breakdown product of PGI2) and 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT). Formation of TXB2 was markedly reduced by imidazole. Tranylcypromine decreased the formation of TXB2 and HHT and inhibited the formation of 6-keto-PGF1 alpha. At low PGH2 concentrations, equal production of TXB2 and 6-keto-PGF1 alpha was observed. However, as PGH2 concentration increased, 6-keto-PGF1 alpha production approached early saturation while TXB2 production increased in a linear fashion. These results suggest that enzymatic formation of TXA2 and PGI2 is a function of substrate availability in the lung. These findings provide a possible explanation for the divergent hemodynamic responses to arachidonic acid infusions at high and low concentrations in the feline pulmonary vascular bed.
D015121:6-Ketoprostaglandin F1 alpha; D000818:Animals; D002415:Cats; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005260:Female; D006880:Hydroxy Acids / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000378:metabolism; D011449:Prostaglandin Endoperoxides / Q000378:metabolism*; D011460:Prostaglandins F / Q000378:metabolism; D011463:Prostaglandins H / Q000378:metabolism*; D013929:Thromboxane B2 / Q000378:metabolism
D005231:Fatty Acids, Unsaturated; D006880:Hydroxy Acids; D011449:Prostaglandin Endoperoxides; D011460:Prostaglandins F; D011463:Prostaglandins H; C008033:12-hydroxy-5,8,10-heptadecatrienoic acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha