Metabolism of prostaglandin endoperoxide by microsomes from cat lung

It has been reported that the prostaglandin (PG) precursor, arachidonic acid, produces divergnet 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, PHG₂, as a substrate. The major products of incubations of PGH₂ with mcirosomes were thromboxane (TX) B₂ (the major metabolite of TXA₂), 6-keto-PGF_1α (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-PGF_1α. At low PGH₂ concentrations, equal production of TXB₂ and 6-keto-PGF_1α was observed. However, as PGH₂ concentration increased, 6-keto-PGF_1α 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.