Age-dependent changes in the synthesis and catabolism of 6 oxo PGE1 and other prostanoids by the rat kidney in vitro.

Synthesis and catabolism of 6 oxo PGE1 was assessed in 100,000 g cell-free supernatant fractions of kidneys obtained from rats aged 20, 34 and 70 days. In addition the release of PGI2, TxA2 (measured as 6 oxo PGF1 alpha and TxB2, respectively), PGE2 and PGF2 alpha from kidney slices prepared from these three groups of rats was determined using specific radioimmunoassays. The conversion of PGI2 to 6 oxo PGE1 (but not 13,14 dihydro 15 oxo PGF2 alpha to 13,14 dihydro 15 oxo PGE2) was detected in supernatant fractions of kidneys from 20 day rats. Slices prepared from the kidneys of these animals spontaneously released significant amounts of three prostanoids (6 oxo PGF1 alpha greater than PGE2 greater than PGF2 alpha greater than TxB2 = 0). No formation of 6 oxo PGE1 from exogenous PGI2 was demonstrated in renal 100,000 g supernates from 34 and 70 day rats even though these supernates avidly oxidised 13,14 dihydro 15 oxo PGF2 alpha to 13,14 dihydro 15 oxo PGE2. In these animals the rank order of prostanoid release from kidney slices was PGE2 greater than 6 oxo PGF1 alpha greater than PGF2 alpha greater than TxB2 = 0. The catabolism of 6 oxo PGE1 is also age-dependent. In 20 and 34 day old rats 6 oxo PGE1 and PGE1 incubated with renal 100,000 g supernates undergo loss of biological activity as determined by the ability to inhibit ADP induced human platelet aggregation. In contrast, kidney 100,000 g supernates prepared from 70 day rats convert 6 oxo PGE1 to an unidentified metabolite with more potent anti-aggregatory activity. The possibility that 6 oxo PGE1 has a biological role in the developing rat kidney is discussed.