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. 1979 Aug;64(2):570–579. doi: 10.1172/JCI109495

Effects of Anion-Transport Inhibitors on NaCl Reabsorption in the Rat Superficial Proximal Convoluted Tubule

Marjory S Lucci 1,2, David G Warnock 1,2
PMCID: PMC372152  PMID: 457869

Abstract

The effects of anion-transport inhibitors on volume reabsorption, and total CO2 concentrations were examined by in vivo microperfusion of superficial proximal convoluted tubules of rats. The luminal perfusion solution was a high-chloride, low-bicarbonate solution like that in the in vivo late proximal tubule. The anion-transport inhibitors were only added to the luminal perfusion solutions.

In tubules perfused with the control high-chloride solution, the rate of volume reabsorption (Jv) was 2.3±0.2 nl/mm·min (n = 18), and the collected total CO2 concentration was 4.0±0.3 mM. Furosemide (3 mM) caused a marked reduction in volume reabsorption to 0.8±0.3 nl/mm·min (n = 20) and only a slight increase in the total CO2 concentration of collected samples of perfusate (7.8±0.5 mM). 0.8 mM acetazolamide caused a more pronounced rise in the collected total CO2 concentrations to 10.7±0.5 mM but only a slight fall in Jv to 1.7±0.3 nl/mm·min (n = 19). Hence, we inferred that inhibition of carbonic anhydrase only partially accounted for the inhibition of Jv by furosemide. 4-acetamido-4′-iso-thiocyanato-stilbene-2,2′-disulphonic acid (0.1 mM), a well-characterized inhibitor of erythrocyte anion exchange mechanisms, also reduced Jv to 1.6±0.3 nl/mm·min (n = 15) without changing the total CO2 concentrations of the collected perfusates (3.6±0.4 mM). The effect of 4-acetamido-4′-iso-thiocyanato-stilbene-2,2′-disulphonic acid on volume reabsorption could not be explained by carbonic anhydrase inhibition because there was no increase in the total CO2 concentration of the collected fluids. Furosemide did not significantly inhibit the rate of tracer glucose efflux out of the tubules, which suggests that the effect of furosemide on volume reabsorption was not a result of some nonspecific depression of active sodium transport. These results are discussed with respect to the possible effects of anion-transport inhibitors on the paracellular shunt pathway, active sodium reabsorption, and neutral sodium chloride transport.

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Selected References

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  1. Aull F., Nachbar M. S., Oppenheim J. D. Chloride self exchange in Ehrlich ascites cells. Inhibition by furosemide and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid. Biochim Biophys Acta. 1977 Dec 15;471(3):341–347. doi: 10.1016/0005-2736(77)90040-2. [DOI] [PubMed] [Google Scholar]
  2. BERLINER R. W. Renal secretion of potassium and hydrogen ions. Fed Proc. 1952 Sep;11(3):695–700. [PubMed] [Google Scholar]
  3. Baer J. E., Beyer K. H. Renal pharmacology. Annu Rev Pharmacol. 1966;6:261–292. doi: 10.1146/annurev.pa.06.040166.001401. [DOI] [PubMed] [Google Scholar]
  4. Bank N., Aynedjian H. S., Weinstein S. W. Effect of intraluminal bicarbonate and chloride on fluid absorption by the rat renal proximal tubule. Kidney Int. 1976 Jun;9(6):457–466. doi: 10.1038/ki.1976.59. [DOI] [PubMed] [Google Scholar]
  5. Barratt L. J., Rector F. C., Jr, Kokko J. P., Seldin D. W. Factors governing the transepithelial potential difference across the proximal tubule of the rat kidney. J Clin Invest. 1974 Feb;53(2):454–464. doi: 10.1172/JCI107579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Berry C. A., Warnock D. G., Rector F. C., Jr Ion selectivity and proximal salt reabsorption. Am J Physiol. 1978 Sep;235(3):F234–F245. doi: 10.1152/ajprenal.1978.235.3.F234. [DOI] [PubMed] [Google Scholar]
  7. Brazy P. C., Gunn R. B. Furosemide inhibition of chloride transport in human red blood cells. J Gen Physiol. 1976 Dec;68(6):583–599. doi: 10.1085/jgp.68.6.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brenner B. M., Keimowitz R. I., Wright F. S., Berliner R. W. An inhibitory effect of furosemide on sodium reabsorption by the proximal tubule of the rat nephron. J Clin Invest. 1969 Feb;48(2):290–300. doi: 10.1172/JCI105985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Burg M., Stoner L., Cardinal J., Green N. Furosemide effect on isolated perfused tubules. Am J Physiol. 1973 Jul;225(1):119–124. doi: 10.1152/ajplegacy.1973.225.1.119. [DOI] [PubMed] [Google Scholar]
  10. Cabantchik Z. I., Rothstein A. The nature of the membrane sites controlling anion permeability of human red blood cells as determined by studies with disulfonic stilbene derivatives. J Membr Biol. 1972 Dec 29;10(3):311–330. doi: 10.1007/BF01867863. [DOI] [PubMed] [Google Scholar]
  11. Cardinal J., Lutz M. D., Burg M. B., Orloff J. Lack of relationship of potential difference to fluid absorption in the proximal renal tubule. Kidney Int. 1975 Feb;7(2):94–102. doi: 10.1038/ki.1975.14. [DOI] [PubMed] [Google Scholar]
  12. Cohen L. H., Mueller A., Steinmetz P. R. Inhibition of the bicarbonate exit step in urinary acidification by a disulfonic stilbene. J Clin Invest. 1978 Apr;61(4):981–986. doi: 10.1172/JCI109023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cousin J. L., Motais R. The role of carbonic anhydrase inhibitors on anion permeability into ox red blood cells. J Physiol. 1976 Mar;256(1):61–80. doi: 10.1113/jphysiol.1976.sp011311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. DEETJEN P. MIKROPUNKTIONSUNTERSUCHUNGEN ZUR WIRKUNG VON FUROSEMID. Pflugers Arch Gesamte Physiol Menschen Tiere. 1965 Jun 2;284:184–190. [PubMed] [Google Scholar]
  15. Duffey M. E., Turnheim K., Frizzell R. A., Schultz S. G. Intracellular chloride activities in rabbit gallbladder: direct evidence for the role of the sodium-gradient in energizing "uphill" chloride transport. J Membr Biol. 1978 Sep 19;42(3):229–245. doi: 10.1007/BF01870360. [DOI] [PubMed] [Google Scholar]
  16. Ehrenspeck G., Brodsky W. A. Effects of 4-acetamido-4'-isothiocyano-2,2-disulfonic stilbene on ion transport in turtle bladders. Biochim Biophys Acta. 1976 Feb 6;419(3):555–558. doi: 10.1016/0005-2736(76)90268-6. [DOI] [PubMed] [Google Scholar]
  17. Frizzell R. A., Dugas M. C., Schultz S. G. Sodium chloride transport by rabbit gallbladder. Direct evidence for a coupled NaCl influx process. J Gen Physiol. 1975 Jun;65(6):769–795. doi: 10.1085/jgp.65.6.769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Frizzell R. A., Field M., Schultz S. G. Sodium-coupled chloride transport by epithelial tissues. Am J Physiol. 1979 Jan;236(1):F1–F8. doi: 10.1152/ajprenal.1979.236.1.F1. [DOI] [PubMed] [Google Scholar]
  19. Frömter E., Gessner K. Effect of inhibitors and diuretics on electrical potential differences in rat kidney proximal tubule. Pflugers Arch. 1975 Jun 26;357(3-4):209–224. doi: 10.1007/BF00585976. [DOI] [PubMed] [Google Scholar]
  20. Frömter E., Rumrich G., Ullrich K. J. Phenomenologic description of Na+, Cl- and HCO-3 absorption from proximal tubules of rat kidney. Pflugers Arch. 1973 Oct 22;343(3):189–220. doi: 10.1007/BF00586045. [DOI] [PubMed] [Google Scholar]
  21. Fülgraff G., Nünemann H., Sudhoff D. Effects of the diuretics furosemide, ethacrynic acid, and chlorothiazide on gluconeogenesis from various substrates in rat kidney cortex slices. Naunyn Schmiedebergs Arch Pharmacol. 1972;273(1):86–98. doi: 10.1007/BF00508082. [DOI] [PubMed] [Google Scholar]
  22. Green R., Giebisch G. Ionic requirements of proximal tubular sodium transport. II. Hydrogen ion. Am J Physiol. 1975 Nov;229(5):1216–1226. doi: 10.1152/ajplegacy.1975.229.5.1216. [DOI] [PubMed] [Google Scholar]
  23. Humphreys M. H. Inhibition of NaCl absorption from perfused rat ileum by furosemide. Am J Physiol. 1976 Jun;230(6):1517–1523. doi: 10.1152/ajplegacy.1976.230.6.1517. [DOI] [PubMed] [Google Scholar]
  24. Hénin S., Cremaschi D. Transcellular ion route in rabbit gallbladder. Electric properties of the epithelial cells. Pflugers Arch. 1975;355(2):125–139. doi: 10.1007/BF00581828. [DOI] [PubMed] [Google Scholar]
  25. Kashgarian M., Warren Y., Levitin H. Micropuncture study of proximal renal tubular chloride transport during hypercapnea in the rat. Am J Physiol. 1965 Sep;209(3):655–658. doi: 10.1152/ajplegacy.1965.209.3.655. [DOI] [PubMed] [Google Scholar]
  26. Klahr S., Yates J., Bourgoignie J. Inhibition of glycolysis by ethacrynic acid and furosemide. Am J Physiol. 1971 Oct;221(4):1038–1043. doi: 10.1152/ajplegacy.1971.221.4.1038. [DOI] [PubMed] [Google Scholar]
  27. Kokko J. P., Burg M. B., Orloff J. Characteristics of NaCl and water transport in the renal proximal tubule. J Clin Invest. 1971 Jan;50(1):69–76. doi: 10.1172/JCI106485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Liedtke C. M., Hopfer U. Anion transport in brush border membranes isolated from rat small intestine. Biochem Biophys Res Commun. 1976 May 23;76(2):579–585. doi: 10.1016/0006-291x(77)90763-x. [DOI] [PubMed] [Google Scholar]
  29. Lucci M. S., Warnock D. G., Rector F. C., Jr Carbonic anhydrase-dependent bicarbonate reabsorption in the rat proximal tubule. Am J Physiol. 1979 Jan;236(1):F58–F65. doi: 10.1152/ajprenal.1979.236.1.F58. [DOI] [PubMed] [Google Scholar]
  30. Malnic G., Mello Aires M., Lacaz Vieira F. Chloride excretion in nephrons of rat kidney during alterations of acid-base equilibrium. Am J Physiol. 1970 Jan;218(1):20–26. doi: 10.1152/ajplegacy.1970.218.1.20. [DOI] [PubMed] [Google Scholar]
  31. Manuel M. A., Weiner M. W. Effects of ethacrynic acid and furosemide on isolated rat kidney mitochondria: inhibition of electron transport in the region of phosphorylation site II. J Pharmacol Exp Ther. 1976 Jul;198(1):209–221. [PubMed] [Google Scholar]
  32. Maude D. L. Mechanism of salt transport and some permeability properties of rat proximal tubule. Am J Physiol. 1970 Jun;218(6):1590–1595. doi: 10.1152/ajplegacy.1970.218.6.1590. [DOI] [PubMed] [Google Scholar]
  33. Maude D. L. The role of bicarbonate in proximal tubular sodium chloride transport. Kidney Int. 1974 Apr;5(4):253–260. doi: 10.1038/ki.1974.34. [DOI] [PubMed] [Google Scholar]
  34. Morgan T., Tadokoro M., Martin D., Berliner R. W. Effect of furosemide on Na+ and K+ transport studied by microperfusion of the rat nephron. Am J Physiol. 1970 Jan;218(1):292–297. doi: 10.1152/ajplegacy.1970.218.1.292. [DOI] [PubMed] [Google Scholar]
  35. Murer H., Hopfer U., Kinne R. Sodium/proton antiport in brush-border-membrane vesicles isolated from rat small intestine and kidney. Biochem J. 1976 Mar 15;154(3):597–604. [PMC free article] [PubMed] [Google Scholar]
  36. Nellans H. N., Frizzell R. A., Schultz S. G. Coupled sodium-chloride influx across the brush border of rabbit ileum. Am J Physiol. 1973 Aug;225(2):467–475. doi: 10.1152/ajplegacy.1973.225.2.467. [DOI] [PubMed] [Google Scholar]
  37. Neumann K. H., Rector F. C., Jr Mechanism of NaCl and water reabsorption in the proximal convoluted tubule of rat kidney. J Clin Invest. 1976 Nov;58(5):1110–1118. doi: 10.1172/JCI108563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Passow H. Anion transport across the red blood cell membrane and the protein in band 3. Acta Biol Med Ger. 1977;36(5-6):817–821. [PubMed] [Google Scholar]
  39. RADTKE H. W., Rumrich G., Kinne-saffran E., Ulrich K. J. Dual action of acetazolamide and furosemide on proximal volume absorption in the rat kidney. Kidney Int. 1972 Feb;1(2):100–105. doi: 10.1038/ki.1972.13. [DOI] [PubMed] [Google Scholar]
  40. Rodicio J. L., Hernando L. Effects and interactions of furosemide and acetazolamide on tubular function in rat kidney. Rev Esp Fisiol. 1977 Jun;33(2):113–118. [PubMed] [Google Scholar]
  41. Rose R. C., Nahrwold D. L. Electrolyte transport by gallbladders of rabbit and guinea pig: effect of amphotericin B and evidence of rheogenic Na transport. J Membr Biol. 1976 Oct 20;29(1-2):1–22. doi: 10.1007/BF01868949. [DOI] [PubMed] [Google Scholar]
  42. Schafer J. A., Patlak C. S., Andreoli T. E. A component of fluid absorption linked to passive ion flows in the superficial pars recta. J Gen Physiol. 1975 Oct;66(4):445–471. doi: 10.1085/jgp.66.4.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Schafer J. A., Patlak C. S., Andreoli T. E. Fluid absorption and active and passive ion flows in the rabbit superficial pars recta. Am J Physiol. 1977 Aug;233(2):F154–F167. doi: 10.1152/ajprenal.1977.233.2.F154. [DOI] [PubMed] [Google Scholar]
  44. Spring K. R., Kimura G. Chloride reabsorption by renal proximal tubules of Necturus. J Membr Biol. 1978 Jan 18;38(3):233–254. doi: 10.1007/BF01871924. [DOI] [PubMed] [Google Scholar]
  45. Thomas R. C. Ionic mechanism of the H+ pump in a snail neurone. Nature. 1976 Jul 1;262(5563):54–55. doi: 10.1038/262054a0. [DOI] [PubMed] [Google Scholar]
  46. Turnberg L. A., Bieberdorf F. A., Morawski S. G., Fordtran J. S. Interrelationships of chloride, bicarbonate, sodium, and hydrogen transport in the human ileum. J Clin Invest. 1970 Mar;49(3):557–567. doi: 10.1172/JCI106266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Ullrich K. J., Capasso G., Rumrich G., Papavassiliou F., Klöss S. Coupling between proximal tubular transport processes. Studies with ouabain, SITS and HCO3-free solutions. Pflugers Arch. 1977 Apr 25;368(3):245–252. doi: 10.1007/BF00585203. [DOI] [PubMed] [Google Scholar]
  48. Ullrich K. J., Radtke H. W., Rumrich G. The role of bicarbonate and other buffers on isotonic fluid absorption in the proximal convolution of the rat kidney. Pflugers Arch. 1971;330(2):149–161. doi: 10.1007/BF00643031. [DOI] [PubMed] [Google Scholar]
  49. Vurek G. G., Warnock D. G., Corsey R. Measurement of picomole amounts of carbon dioxide by calorimetry. Anal Chem. 1975 Apr;47(4):765–767. doi: 10.1021/ac60354a024. [DOI] [PubMed] [Google Scholar]
  50. Wilczewski T. W., Olson A. K., Carrasquer G. Effect of amiloride, furosemide, and ethacrynic acid on Na transport in the rat kidney. Proc Soc Exp Biol Med. 1974 Apr;145(4):1301–1305. doi: 10.3181/00379727-145-38001. [DOI] [PubMed] [Google Scholar]
  51. Windhager E. E., Giebisch G. Proximal sodium and fluid transport. Kidney Int. 1976 Feb;9(2):121–133. doi: 10.1038/ki.1976.16. [DOI] [PubMed] [Google Scholar]
  52. Yoshida A., Yamada T., Koshikawa S. Effect of diuretics on energy metabolism. Biochem Pharmacol. 1971 Aug;20(8):1933–1942. doi: 10.1016/0006-2952(71)90392-3. [DOI] [PubMed] [Google Scholar]

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