Studies of the mechanisms involved in the fate of prostacyclin (PGI2) and 6-keto-PGF1alpha 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-PGF1alpha 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 beta-NAD, [3]H-PGI2 was extensively degraded into at least one metabolite, while [3]H-6-keto-PGF1alpha was only minimally metabolized. However, on passage through isolated perfused rat lungs, neither [3]H-PGI2 nor [3]H-6-keto-PGF1alpha 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 ot the structure-activity requirements necessary for pulmonary transport and subsequent metabolism.
D000818:Animals; D002855:Chromatography, Thin Layer; D003911:Dextrans / Q000494:pharmacology; D011464:Epoprostenol / Q000097:blood / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D009243:NAD / Q000494:pharmacology; D010477:Perfusion; D011453:Prostaglandins / Q000378:metabolism*; D011460:Prostaglandins F / Q000097:blood / Q000378:metabolism*; D011652:Pulmonary Circulation; D051381:Rats
D003911:Dextrans; D011453:Prostaglandins; D011460:Prostaglandins F; D009243:NAD; D011464:Epoprostenol