Competition of organic anions for furosemide and p-aminohippurate secretion in the rabbit.
The excretion of [14C]- or [35S]furosemide and [3H]-p-aminohippurate (PAH) injected within 4 min into the left renal artery of rabbits was measured under brisk mannitol diuresis. The estimated rate of furosemide secretion during the first pass through the left kidney was lower than that of PAH when neither of the two transport processes were saturated: 7.9 and 12.9% of the total amounts injected were secreted per minute, respectively. Different competitive inhibitors were injected i.v. Probenecid (50 mg/kg) inhibited furosemide and PAH secretion by 95 and 80%, respectively. Pyrazinoate at plasma concentrations of 3 to 5 mM had no effect on either anion. Indomethacin (10 mg/kg) depressed furosemide secretion by 24% but had no effect on PAH secretion. PAH at a concentration of 9 to 17 mM in plasma depressed furosemide secretion by only 44 to 66%. Furosemide did not inhibit PAH secretion when infused into the left renal artery at a rate 5000 times higher than PAH. It was concluded that furosemide is secreted partly by the transport system secreting PAH, for which it had only a low affinity, and partly by a transport system for which indomethacin had some affinity. This latter transport system, in turn, differs from that secreting pyrazinoate. The furosemide-induced natriuresis, in both kidneys, was proportional to the urinary excretion rate of furosemide until the fractional excretion of Na+ reached an apparent maximum of 20 to 30%.
J
J
Bidiville
F
F
Roch-Ramel
D000618:Aminohippuric Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005260:Female; D005665:Furosemide / Q000378:metabolism* / Q000494:pharmacology; D005919:Glomerular Filtration Rate; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D011339:Probenecid / Q000494:pharmacology; D011718:Pyrazinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D011817:Rabbits; D013997:Time Factors; D014316:Tritium; D010130:p-Aminohippuric Acid / Q000378:metabolism*
D000618:Aminohippuric Acids; D014316:Tritium; D011718:Pyrazinamide; C005296:pyrazinoic acid; D005665:Furosemide; D011339:Probenecid; D007213:Indomethacin; D010130:p-Aminohippuric Acid