Studies of the mechanisms involved in the fate of prostacyclin (PGI2) and 06-keto-PGF1α in the pulmonary circulation

We have investigated the metabolism of 3]H-prostaglandin (PG)I₂ and its non-enzymatic breakdown product 3]H-6-keto-PGF_1α by rat pulmonary tissue and their possible uptake and metabolism upon passage through the isolated perfused rat lung. When incubated with rat lung homogenate in the presence of β-NAD, 3]H-PGI₂ was extensively degraded into at least one metabolite, while 3]H-6-keto-PGF_1α was only minimally metabolized. However, on passage through isolated perfused rat lungs, neither 3]H-PGI₂ nor 3]H-6-keto-PGF_1α were removed from the circulation into the lung or degraded. This demonstration that PGI₂ is not a substrate for the transport system for the removal of PGs from the circulation into the lung further illustrates that this system is a critical determinant for the pulmonary inactivation of circulating prostaglandins. The experimental findings are discussed in reference to the structure-activity requirements necessary for pulmonary transport and subsequent metabolism.