Renal tubular transport of prostaglandins: inhibition by probenecid and indomethacin.
With use of the Sperber technique in chickens, labeled prostaglandin E2 and F2alpha were infused and resulted in renal tubular excretion of the label into the urine. A labeled metabolite, 12,14-dihydro,15-keto-PGF2alpha, was infused exogenously and this label was also excreted by active tubular transport. Tubular excretion of the label from PGE2, PGF2alpha, and 13,14-dihydro,15-keto-PGF2alpha was inhibited by probenecid, indomethacin, and PAH. The PAH was 10 times weaker as an inhibitor than probenecid and indomethacin. These results indicate that the prostaglandins are actively transported across the renal tubule by the classic anionic transport system which transports PAH. Since the transport of the prostaglandins is blocked by nonsteroidal anti-inflammatory agents such as indomethacin, the anti-inflammatory action of indomethacin may be produced not only by the inhibition of prostaglandin synthesis but also by restriction of the distribution of endogenous prostaglnadins. Thin-layer chromatography of an ethyl acetate extract of urine collected during infusion of [3H]PGF2alpha revealed three discrete radioactive peaks, one of which corresponded to authentic PGF2alpha. This signified tubular excretion of PGF2alpha. One metabolite in the ethyl acetate extract was found to be of renal origin.
D000818:Animals; D001693:Biological Transport, Active; D002645:Chickens / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology*; D007684:Kidney Tubules / Q000378:metabolism*; D011339:Probenecid / Q000494:pharmacology*; D011458:Prostaglandins E / Q000378:metabolism*; D011460:Prostaglandins F / Q000378:metabolism*; D011465:Prostaglandins, Synthetic / Q000378:metabolism
D011458:Prostaglandins E; D011460:Prostaglandins F; D011465:Prostaglandins, Synthetic; D011339:Probenecid; D007213:Indomethacin