Pflügers Archiv

, Volume 400, Issue 3, pp 241–249 | Cite as

Secretion and contraluminal uptake of dicarboxylic acids in the proximal convolution of rat kidney

  • K. J. Ullrich
  • H. Fasold
  • G. Rumrich
  • S. Klöss
Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands


The transport of dicarboxylic acids in the proximal convolution was investigated by measuring: a) the zero net flux transtubular concentration difference ofdl-methyl-succinate, b) its 2-s influx from the interstitium into tubular cells, and c) its 3.5-s efflux from the tubular lumen. With the first method a luminal concentration exceeding the peritubular concentration was observed, thus indicating a net active transtubular secretion of this slowly metabolized substance.

All transport steps, luminal and contraluminal, as well as the overall transport, were Na+-dependent and inhibited by lithium (apparentKi ≈ 1.8 mmol/l). The overall transport of methylsuccinate, as well as the contraluminal influx into proximal tubular cells, could be inhibited by paraaminohippurate and H2-DIDS with an apparentKi of ≈ 1.8 mmol/l, by taurocholate with an apparentKi ≈ 3.` mmol/l and by pyruvate with an apparentKi ≈ 5 mmol/l, but not by sulfate, thiosulfate,l-lactate, oxalate and urate. As judged from the inhibition of contraluminal methylsuccinate influx by 48 dicarboxylic acids (aliphatic and aromatic), a specificity pattern was observed similar to that of inhibition of luminal efflux of 2-oxoglutarate [22]: a preference of dicarboxylates in the transconfiguration with a chain length of 4–5 carbons; little change in the inhibitory potency with CH3, OH−, SH−and O=, but strong reduction with a NH 3 + in the 2 position; only a small reduction of inhibitory potency with 2,3 disubstituted SH and OH analogs; preference of the dicarboxylic benzene in the 1,4 position and of the diacetyl benzene in the 1,2 position. The data indicate a Na+-dependent dicarboxylic transport system at the contraluminal cell side of the proximal tubule which is very similar to the luminal transport system for dicarboxylic acids.

Key words

Basolateral cell membrane Methylsuccinate-transport 2-Oxolutarate-transport Citrate-transport Lithium 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Balagura S, Stone WJ (1967) Renal tubular secretion of α-ketoglutarate in dog. Am J Physiol 212:1319–1326Google Scholar
  2. 2.
    Burckhardt G (1984) Sodium-dependent dicarboxylate transport in rat renal basolateral membrane vesicles. Pflügers Arch (submitted)Google Scholar
  3. 3.
    Cohen JJ, Wittmann E (1963) Renal utilization and excretion of α-ketoglutarate in dog: effect of alkalosis. Am J Physiol 204:795–811Google Scholar
  4. 4.
    Cohen RD, Prout RES (1965) Studies on renal transport of citrate using14C-citrate. Clin Sci 28:487–497Google Scholar
  5. 5.
    Crawford MA, Milne MD, Scribner BH (1959) The effects of changes in acid-base balance on urinary citrate in the rat. J Physiol 149:413–423Google Scholar
  6. 6.
    Copenhaver JH, Forster RP (1958) Displacement characteristics of intracellularly accumulated p-aminohippurate in mammalian renal transport system in vitro. Am J Physiol 195:327–330Google Scholar
  7. 7.
    Cross RJ, Taggart JV (1950) Renal tubular transport: accumulation of p-aminohippurate by rabbit kidney slices. Am J Physiol 161:181–190Google Scholar
  8. 8.
    Fritzsch G, Haase W, Rumrich G, Fasold H, Ullrich KJ (1984) A stopped flow capillary perfusion method to evaluate contraluminal transport parameters of methylsuccinate from interstitium into renal proximal tubular cells. Pflügers Arch 400:250–256Google Scholar
  9. 9.
    Grollmann AP, Harrison HC, Harrison HE (1961) The renal excretion of citrate. J Clin Invest 40:1290–1296Google Scholar
  10. 10.
    Häberle D, Wahlländer A, Sies H (1979) Assessment of the kidney function in maintenance of plasma glutathione concentration and redox state in anaesthetized rats. FEBS Lett 108:335–340Google Scholar
  11. 11.
    Herndon RF, Freeman S (1958) Renal citric acid utilization in the dog. Am J Physiol 192:369–372Google Scholar
  12. 12.
    Kragh-Hansen U, Jørgensen KE, Sheikh MI (1982a) The use of potential sensitive cyanine dye for studying ion-dependent electrogenic renal transport of organic solutes. Spectrophotometric measurements. Biochem J 208:359–368Google Scholar
  13. 13.
    Kragh-Hansen U, Jørgensen KE, Sheikh MI (1982b) The use of potential sensitive cyanine dye for studying ion dependent electrogenic renal transport of organic solutes. Uptake ofl-malate andd-malate by luminal membrane vesicles. Biochem J 208:369–376Google Scholar
  14. 14.
    Kippen I, Hirayama B, Klinenberg JR, Wright EM (1979) Transport of tricarboxylic acid cycle intermediates by membrane vesicles from renal brush border. Proc Natl Acad Sci USA 76:3397–3400Google Scholar
  15. 15.
    Löw I, Friedrich T, Burckhardt G (1984) Properties of an anion exchanger in rat renal basolateral membrane vesicles. Am J Physiol 246 (in press)Google Scholar
  16. 16.
    Pakarinen A, Runeberg L (1969) Effects of phenolsul-phonphthalein and probenecid on the uptake and utilization of citrate and α-ketoglutarate by kidney in vitro. Biochem Pharmacol 18:2439–2452Google Scholar
  17. 17.
    Pfaller W (1982) Structure function correlation on rat kidney. In: Advances in anatomy, embryology and cell biology, vol 70. Springer, Berlin Heidelberg New YorkGoogle Scholar
  18. 18.
    Pritchard JB, Renfro JL (1983) Renal sulfate transport at the basolateral membrane is mediated by anion exchange. Proc Natl Acad Sci USA 80:2603–2607Google Scholar
  19. 19.
    Rankin BB, Curthoys NP (1982) Evidence for the renal paratubular transport of glutathione. FEBS Lett 147:193–196Google Scholar
  20. 20.
    Sellek BH, Cohen JJ (1965) Specific localization of α-ketoglutarate uptake to dog kidney and liver in vivo. Am J Physiol 208:24–37Google Scholar
  21. 21.
    Sheikh MI, Kragh-Hansen U, Jørgensen KE, Røigaard-Petersen H (1982) An efficient method for the isolation and separation of basolateral membrane and luminal membrane vesicles from rabbit kidney cortex. Biochem J 208:377–382Google Scholar
  22. 22.
    Sheridan E, Rumrich G, Ullrich KJ (1984) Reabsorption of dicarboxylic acids from the proximal convolution of rat kidney. Pflügers Arch 399:18–28Google Scholar
  23. 23.
    Silbernagl S, Pfaller W, Heinle H, Wendel A (1978) Topology and function of ranal γ-glutamyl transpeptidase. In: Sies H, Wendel A (eds) Functions of glutathione in liver and kidney. Springer, Berlin Heidelberg New YorkGoogle Scholar
  24. 24.
    Simpson DP (1983) Citrate excretion: a window on renal metabolism. Am J Physiol 244:F223-F234Google Scholar
  25. 25.
    Sperber I (1959) Secretion of organic anions in the formation of urine and bile. Pharmacol Rev 11:109–134Google Scholar
  26. 26.
    Ullrich KJ, Rumrich K, Klöss S (1980) Monocarboxylic acid (d-lactate) and dicarboxylic acid (malonate) transport in the proximal convolution of the rat kidney. Pflügers Arch 384:R8Google Scholar
  27. 27.
    Ullrich KJ, Rumrich G, Klöss S (1982) Reabsorption of monocarboxylic acids in the proximal tubule of the rat kidney. I. Transport kinetics ofd-lactate, Na+-dependence, pH-dependence and effect of inhibitors. Pflügers Arch 395: 212–219Google Scholar
  28. 28.
    Ullrich KJ, Murer H (1982) Sulphate and phosphate transport in the renal proximal tubule. Phil Trans R Soc Lond B 299: 549–558Google Scholar
  29. 29.
    Ullrich KJ, Burckhardt G (1983) Involvement of a common contraluminal anion exchanges system in rat proximal tubular inorganic and organic anion transport. Abstr. IUPS, 19. Int. Congress Sydney, p 70Google Scholar
  30. 30.
    Vishwakarma P, Lotspeich WD (1959) The excretion ofl-malic acid in relation to the tricarboxylic acid cycle in the kidney. J Clin Invest 38:414–423Google Scholar
  31. 31.
    Vishwakarma P, Lotspeich WD (1960) Excretion ofl-malic acid in the chicken. Am J Physiol 198:819–823Google Scholar
  32. 32.
    Vishwakarma P (1962) Reabsorption and secretion ofl-malic acid in kidney proximal tubule. Am J Physiol 202:572–576Google Scholar
  33. 33.
    Wright SH, Kippen I, Klinenberg JR, Wright EM (1980) Specificity of the transport system for tricarboxylic acid cycle intermediates in renal brush borders. J Membr Biol 57:73–82Google Scholar
  34. 34.
    Wright SH, Krasne S, Kippen I, Wright EM (1981) Na+-dependent transport of tricarboxylic acid cycle intermediates by renal brush border membranes. Effect on fluorescence of a potential sensitive cyanine dye. Biochim Biophys Acta 640:767–778Google Scholar
  35. 35.
    Wright EM, Wright SH, Hirayama B, Kippen I (1982) Interactions between lithium and renal transport of Krebs-cycle intermediates. Proc Natl Acad Sci USA 79:7514–7517Google Scholar
  36. 36.
    Wright SH, Kippen I, Wright EM (1982) Effect of pH on the transport of Krebs-cycle intermediates in renal brush border membranes. Biochim Biophys Acta 684:287–290Google Scholar
  37. 37.
    Wittner M, Weidtke C, Schlatter E, Di Stefano A, Greger R (1984) Substrate utilization in the isolated perfused cortical thick ascending limb of rabbit nephron. Pflügers Arch (submitted)Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • K. J. Ullrich
    • 1
  • H. Fasold
    • 2
  • G. Rumrich
    • 1
  • S. Klöss
    • 1
  1. 1.Max-Planck-Institut für BiophysikFrankfurt/Main 70Federal Republic of Germany
  2. 2.Institut für Biochemie der J. W. Goethe-UniversitätFrankfurt/Main 70Federal Republic of Germany

Personalised recommendations