Stop-flow studies on tubular transport of uric acid in rats.
A stop-flow technique using pyrazinoic acid(PZO)-treated and -untreated rats was devised to evaluate drug effects on bi-directional transport of uric acid in the tubules. Constant venous infusion of test drugs to PZO-untreated rats was used to estimate their inhibitory effects on urate secretion, while their inhibitory effects on urate reabsorption was studied by intravenous administration as a bolus to PZO-treated rats. Probenecid, tienilic acid and R-(+)-enantiomer of S-8666, which is the uricosuric component of a new uricosuric diuretic, decreased the (Tua/Pua)/(Tin/Pin) value in the distal and proximal tubules by inhibiting urate secretion in PZO-untreated rats. On the other hand, all of these drugs increased the (Tua/Pua)/(Tin/Pin) value in the tubules in PZO-treated rats, which suggested that they also inhibited the reabsorptive flux of urate. This stop-flow technique in rat kidneys showed the possibilities of bi-directional inhibition by these drugs of urate transport in the tubules.
Shinosaki
T
T
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Yonetani
Y
Y
D000818:Animals; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D011339:Probenecid / Q000494:pharmacology; D011718:Pyrazinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013449:Sulfonamides / Q000494:pharmacology; D013989:Ticrynafen / Q000494:pharmacology; D014527:Uric Acid / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000652:urine*
D013449:Sulfonamides; C052960:S 8666; D014527:Uric Acid; D011718:Pyrazinamide; C005296:pyrazinoic acid; D013989:Ticrynafen; D011339:Probenecid