Metabolism of prostaglandin E2 in the isolated perfused kidney of the rabbit.

In the Krebs-perfused rabbit isolated kidney, [3H]PGE2 (5 microCi, 165 Ci/mmole) was infused intra-artially for 5 min; venous and urinary effluents were collected every 2 min for 20 min. Efflux of radioactive material peaked at 8 min and declined thereafter. The kidney retained 35% of the infused 3H. Samples were extracted for acidic lipids; PGE2, PGF2 alpha and metabolites were separated by TLC and quantified by a radiometric method. Efflux of [3H]PGF2 alpha into urinary and venous outflows increased progressively over the first 12 min and then plateaued for the remaining 4 min. By 12 min, conversion of [3H]PGE2 to [3H]PGF2 alpha was 70 and 80% as determined by radiolabeled products recovered in the urinary and venous effluents respectively. Estimates of total conversion of [3H]PGE2 to [3H]PGE2 alpha were 62 and 52% of the radiolabeled material exiting in the urinary and venous effluents respectively. The 15-keto and 13,14-dihydro-15-keto metabolites of [3H]PGF2 alpha appeared in the urine but were not found in the venous outflow. We conclude that PGE-9-ketoreductase (PGE-9KRD) activity is high in the rabbit isolated perfused kidney. Further, the extent of conversion of PGE2 to PGF2 alpha and metabolism of newly formed PGF2 alpha may differ within the vascular and tubular compartments of the kidney. PGE-9KRD activity may be important in the regulation of renal vascular tone, compliance of veins, and salt and water balance.