Prostaglandin uptake and metabolism by the perfused rat liver

Abstract

Summary1. The prostaglandins are C20 unsaturated fatty acids which exhibit diverse physiological effects of short duration. We have invesitigated the speed of removal of PGE1 and PGFia from the circulating blood and their subsequent metabolism by the isolated perfused rat liver. 2. Following either a single injection of radiolabelled PGE1 or PGFia into the hepatic artery or portal vein, or recirculation of prostaglandins through the liver for 2-5 h, the distribution of radioactivity within extracts of bile, blood and liver was determined. The nature of the radioactive products of metabolism was inferred by comparison of the distribution of radioactivity after injecting carbon and tritium labelled standards, and by thin-layer chromatography, gas-liquid chromatography, ultraviolet and bioassay analysis.3. A single injection of 1-1"C PGE, indicated that the liver could efficiently remove 89-95% of circulating PGE1 on a single passage. Biliary excretion was excluded as a major route for elimination of unchanged PGE1, because only 0-3-0-8% of the injected radioactiviity was detected in the bile. During recirculation of 1-14C PGEI, 11-19% of the injected radioactivity was detected as exchanged "4CO2. The radioactivity detected within liver was identified with further fragments resulting from decarboxylation of PGEI, which were incorporated into fatty acids and then phospholipids.4. Studies with 5,6-3H PGE,, and comparison with the results obtained using 1-"C PGE1, revealed a 30-fold increase in the percentage of radioactivity excreted into the bile, suggesting that biliary excretion may be a major route for elimination of compounds smaller than C20 prostaglandin. Evidence that the cyclopentane ring was intact was inferred by formation of a PGB compound on treatment with alkali; similar biliary excretion of 9-3H PGFia also occurred. In addition, the increased radioactivity detected within the liver (37%) and blood (43 %) after a single injection of 5,6-3H PGE, had the solvent partition and thin-layer chromatography properties of PGE1, but were associated with a less polar compound smaller than the C20 parent structure.5. These results indicate rapid uptake of circulating prostaglandins by the rat liver. Decarboxylation of prostaglandins resul;ts in pharmacological inactivation. The products are excreted into the bile and venous effluent. These processes would curtail the duration of effects following prostaglandin injection.

Stimulation of water and sodium secretion and inhibition of glucose absorption from the rat jejunum during intraarterial infusions of prostglandins.

“…As much as 85 to 90 % of PGE1 is inactivated by a single pass through the rat liver (Dawson, Jessup, McDonald-Gibson, Ramwell, and Shaw, 1970) and PGE1, E2 and F2, are also inactivated in the lungs of the guineapig,cat and dog (Piper, Vane, and Wyllie, 1970;Ferreira and Vane, 1967). Isoprenaline is also inactivated relatively rapidly by catechol 0-methyltransferase in the rat (Hertting, 1964) so it was necessary to devise a technique of infusing these compounds directly into the arterial blood supply of the intestine.…”

Characterization of prostaglandin‐F 2α‐binding sites on rat hepatocyte plasma membranes

“…Yet, PG are rapidly metabolized by hepatocytes [3, 48, 491. During one liver passage, more than 90% of exogenously added PG is degraded [50] (Piischel, G. P., Hulsmann, M. and Jungermann, K., unpublished results).…”

Prostaglandin E₁: Its Effects on Hepatic Circulation in Dogs

“…Dawson et al (10) suggested on the basis of isolated perfusion experiments with l4C-labeled PGE, rapid uptake and even decarboxylation of prostaglandin by rat liver tissue. Our data in dogs, are compatible with and add further weight to these investigations in cats and rats, that the liver appears to be an important site of inactivation of prostaglandins.…”