Fate of exogenous and endogenous prostaglandins D2 and E2 in the perfused rat liver.

The degradation of radiolabelled exogenous PGD2 and PGE2 was compared to that of endogenous labelled prostaglandins synthesized after stimulation with PMA in the perfused rat liver. With exogenous PGD2 and PGE2 the same degradation products were found in the perfused liver as in hepatocyte primary cultures. The major metabolite of PGD2 was dinor-PGD2 while tetranor-PGE1 was the main degradation product of PGE2. Some polar metabolites and tritiated water were also formed. The metabolites detected with endogenous prostaglandins were similar to those obtained with exogenous PGD2. Over 99% of the labelled prostaglandins were degraded in the recirculating perfusion within 40 min. In the open perfusion system, 95% of endogenous PGD2 was calculated to be degraded after a single passage through the liver, which suggests that hepatocytes play an important role in the removal of biologically active prostaglandins.