Metabolism of prostaglandin a: 1. The kidney cortex as a major site of PGA 2 degradation

Abstract

The antihypertensive and natriuretic prostaglandin A 2 (medullin) has been isolated and identified in rabbit renal papilla. Since PGA 2, unlike prostaglandin F 2 (PGE 2) and prostaglandin F 2α (PGF 2α), is not metabolized by the lung, studies were undertaken to determine if the site of PGA 2 metabolism is in the renal cortex where its primary vasodilatory and natriuretic effects occur. In in vitro experiments, homogenates of renal cortex and outer medulla were incubated with 3H-PGA 2 (0.2 μc, 20 μg) at 37°C for 30 minutes. A metabolite(s) less polar than 3H-PGA 2 was observed following silicic acid chromatography of acidic lipid extracts of cortical, but not outer medullary homogenates. In in vivo studies, 3H-PGA 2 (2 μc, 50 μg) was injected into the renal artery of the rabbit and blood withdrawn from the ipsilateral renal vein. At least three less polar major metabolites of PGA 2 were observed in the plasma within 15 seconds following injection. No appreciable 3H-PGA 2 was observed in venous plasma 30 seconds following injection of 3H-PGA 2. In contrast to plasma, the major urinary metabolites were more polar than PGA 2. The present study reveals that PGA 2 is almost completely metabolized in a single passage through the rabbit kidney suggesting this organ is a major site of PGA 2 metabolism.