Stop-Flow Studies on Tubular Transport of Uric Acid in Rats

  • Toshihiro Shinosaki
  • Yukio Yonetani
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 253A)


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.


Uric Acid Proximal Tubule Test Drug Tienilic Acid Tubular Transport 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Bechwood, E. C., W. O. Berndt and G. H. Mudge: Stop-flow analysis of tubular transport of uric acid in rabbits. Am. J. Physiol., 207, 1265–1272 (1964).Google Scholar
  2. 2.
    Lemieux, G., Kiss, A., Vinay, P. and Michaud, G.: Nature of the uricosuric effect of tienilic acid, a new diuretic. Kidney Int., 12, 104–114 (1977).PubMedCrossRefGoogle Scholar
  3. 3.
    Lemieux, G., Vinay, A., Gougoux, A. and Michaud, G.: Nature of the uricosuric action of benziodarone. Am. J. Physiol., 224(6), 1440–1449 (1973).PubMedGoogle Scholar
  4. 4.
    Vurek, G. G. and Pegram, S. E.: Fluometric method for the determination of nanogram quantities for inulin. Anal. Biochem., 16, 409–419 (1966).CrossRefGoogle Scholar
  5. 5.
    Yonetani, Y., Iwaki, K., Shinosaki, T., Kawase-Hanafusa, A., Harada, H. and Arthur A, van ES: A new uricosuric diuretic, S-8666, in rats and chimpanzees. Japan. J. Pharmacol., 43, 389–398 (1987).CrossRefGoogle Scholar
  6. 6.
    Yonetani, Y., Iwaki, K., Ishii, M., and Harada, H.: A new diuretic that does not reduce renal handling of uric acid in rats, S-8666. Japan. J. Pharmacol., 43, 399–405 (1987).CrossRefGoogle Scholar
  7. 7.
    Harada, H. and Yonetani, Y.: 5-Sulfamoyl-2, 3-dihydrobenzofuran-2-carboxylic acid derivatives: S-8666, a favorable candidate with uricosuric and diuretic activities. Drugs of the Future, 13, 257–264 (1988).Google Scholar
  8. 8.
    Greger. R., Lang, F., and Deetjen, P.: Handling of uric acid by the rat kidney. I. Pflüngers Arch., 324, 279–287 (1971).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Toshihiro Shinosaki
    • 1
  • Yukio Yonetani
    • 1
  1. 1.Shionogi Research LaboratoriesShionogi & Co., Ltd.Fukushima-ku, Osaka 553Japan

Personalised recommendations