Pflügers Archiv

, Volume 403, Issue 1, pp 90–96 | Cite as

Short term effect of low doses of tri-iodothyronine on proximal tubular membrane Na−K-ATPase and potassium permeability in thyroidectomized rats

  • Giovambattista Capasso
  • J. -T. Lin
  • Natale G. De Santo
  • Rolf Kinne
Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands


Tri-iodothyronine (T3), even when administered for short time and at low doses, induces a large increase in the isotonic fluid reabsorption (Jv) in proximal tubules of thyroidectomized rats (TX). In order to investigate the role of the Na−K-ATPase in this process, we measured the Na−K-ATPase activity in early proximal convoluted tubules (S1) and proximal straight tubules (S2) microdissected from TX rats and rats treated with low doses of T3 (10 μg/kg body wt), either for 3 days (TX+3T3) or for 7 days (TX+7T3). In both segments no changes in Na−K-ATPase activity were found in TX+3T3 rats versus TX rats, while an increase was registered in TX+7T3 rats. Using micropuncture techniques,Jv measured on the same tubular segments increased by 68% in TX+3T3 rats versus TX. Thus, no correlation betweenJv and Na−K-ATPase activity measured in vitro could be detected after short term treatment of TX rats with T3. Na−K-ATPase activity in vivo is also regulated by the potassium permeability of the membrane, which might be altered by tri-iodothyronine. This hypothesis was tested by perfusing intraluminally and peritubularly proximal tubules of TX rats with the K ionophore, valinomycin (1 μg/ml). In the dual perfusion experiments valinomycin elicited 40% of the action induced onJv by 3 days treatment with T3. On the other hand, no further increase inJv was recorded when valinomycin was applied in TX rats pretreated with T3. Taken together, the in vivo and in vitro experiments suggest that low doses of T3 administered for short time to TX rats do not affect Na−K-ATPase activity directly, but stimulate the in vivo activity indirectly by an increase in thek permeability of proximal tubular cell membranes. This latter effect would explain the increase inJv through an increase in the driving force for sodium entry into the cell.

Key words

Tri-iodothyronine Rat proximal tubule Na−K-ATPase Valinomycin Isotonic fluid reabsorption Potassium permeability 


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  1. 1.
    Adamson LF, Ingbar SH (1967) Selective alteration by triiodothyronine of amino acid transport in embryonic bone. Endocrinology 81:1362–1371Google Scholar
  2. 2.
    Andreoli TE, Tieffenberg M, Tosteson DC (1967) The effect of valinomycin on the ionic permeability of thin lipid membranes. J Gen Physiol 50:2527–2545Google Scholar
  3. 3.
    Asano Y, Liberman UA, Edelman IS (1974) Thyroid thermogenesis. Relationship between Na+-dependent respiration and Na+−K+ adenosine triphosphatase activity in rat skeletal muscle. J Clin Invest 57:368–379Google Scholar
  4. 4.
    Berry CA (1982) Heterogeneity of tubular transport processes in the nephron. Ann Rev Physiol 44:181–201Google Scholar
  5. 5.
    Burg M, Grantham J, Abramow M, Orloff J (1966) Preparation and study of fragments of single rabbit nephrons. Am J Physiol 210:1293–1298Google Scholar
  6. 6.
    Capasso G, Kinne-Saffran E, De Santo MG, Kinne R (1984) Regulation of volume reabsorption by thyroid hormones in the proximal tubule of rat: Minor role of luminal sodium permeability. Pflügers Arch 403:97–104Google Scholar
  7. 7.
    De Santo NG, Capasso G, Kinne R, Moewes B, Carella C, Anastasio P, Giordano C (1982) Tubular transport processes in proximal tubules of hypothyroid rats. Lack of relationship between thyroidal dependent rise of isotonic fluid reabsorption and Na+−K+-ATPase activity. Pflügers Arch 394:294–301Google Scholar
  8. 8.
    De Santo NG, Capasso G, Paduano C, Giordano C (1980) Tubular transport processes in proximal tubules of hypothyroid rats. Micropuncture studies on isotonic fluid, amino acid and buffer reabsorption. Pflügers Arch 384:117–122Google Scholar
  9. 9.
    Doucet A, Katz AI, Morel F (1979) Determination of Na−K-ATPase activity in single segments of mammalian nephron. Am J Physiol 237 (2):F105-F113Google Scholar
  10. 10.
    Edelman IS (1981) Receptor and effectors in hormone action on the kidney. Am J Physiol 242:F333-F339Google Scholar
  11. 11.
    Espinosa RE, Keller MJ, Yusufi AHK, Dousa T (1984) Effect of thyroxine administration on phosphate transport across renal cortical brush border membrane. Am J Physiol 246:F133-F139Google Scholar
  12. 12.
    Garg LC, Knepper MA, Burg MB (1981) Mineralocorticoid effects on Na−K-ATPase in individual nephron segments. Am J Physiol 240:F536-F544Google Scholar
  13. 13.
    Garg LC, Mackie S, Tisher CC (1982) Effect of low potassium diet on Na−K-ATPase in rat nephron segments. Pflügers Arch 394:113–117Google Scholar
  14. 14.
    Garg LC, Mackie S, Tisher CC (1982) Site of action of thyroid hormone on Na−K-ATPase in rat nephron segments. Kidney Int 21:274Google Scholar
  15. 15.
    Gertz KH (1963) Transtubuläre Natriumchloridflüsse und Permeabilität für Nichtelektrolyte im proximalen und distalen Konvolut der Rattenniere. Pflügers Arch 276:336–356Google Scholar
  16. 16.
    Goldfine ID, Simons CG, Ingbar SH (1975) Stimulation of uptake of α-aminoisobutyric acid in rat thymocytes byl-triiodothyronine: A comparison with insulin and dibuturyl cyclic AMP. Endocrinology 96:802–805Google Scholar
  17. 17.
    Györy AZ (1971) Reexamination of the split oil droplet method as applied to kidney tubules. Pflügers Arch 324:328–343Google Scholar
  18. 18.
    Haber RS, Loeb JN (1982) Effect of 3,5,3′-triiodothyronine treatment on potassium efflux from isolated rat diaphragm: Role of increased permeability in the thermogenic response. Endocrinology 111:1217–1223Google Scholar
  19. 19.
    Holmes EW, Di Scala VA (1970) Studies on the exaggerated natriuretic response to a saline infusion in the hypothyroid rat. J Clin Invest 49:1224–1236Google Scholar
  20. 20.
    Katz AI, Lindheimer MD (1973) Renal sodium and potassium activated adenosine triphosphatase and sodium reabsorption in the hypothyroid rat. J Clin Invest 52:976–804Google Scholar
  21. 21.
    Kinne R, Schmitz JE, Kinne-Saffran E (1971) The localization of the Na+−K+-ATPase in the cells of rat kidney cortex. A study on isolated plasma membranes. Pflügers Arch 321:191–206Google Scholar
  22. 22.
    Koefed-Johnson V, Ussing HH (1958) The nature of the frog skin potential. Acta Physiol Scand 42:298–308Google Scholar
  23. 23.
    Lo CS, Lo MT (1979) Time course of renal response to triiodothyronine in the rat. Am J Physiol 236:F9-F13Google Scholar
  24. 24.
    Mernissi GE, Doucet A (1983) Short-term effect of aldosterone on renal sodium transport and tubular Na−K-ATPase in the rat. Pflügers Arch 399:139–146Google Scholar
  25. 25.
    Michael UF, Barenberg KL, Chavez R, Vaamonde CA, Papper S (1972) Renal handling of sodium and water in the hypothyroid rat. Clearance and micropuncture studies. J Clin Invest 51:1405–1412Google Scholar
  26. 26.
    Philipson KD, Edelman IS (1977) Thyroid hormone control of Na+−K+-ATPase and K+ dependent phosphatase in the rat heart. Am J Physiol 232:C196-C201Google Scholar
  27. 27.
    Pliam MB, Goldfine ID (1977) High affinity thyroid hormone binding sites on purified rat liver plasma membrane. Biochem Biophys Res Commun 79:166–172Google Scholar
  28. 28.
    Schmidt U, Dubach UC (1969) Activity of (Na+−K+)-stimulated adenosine-triphosphatase in rat nephron. Pflügers Arch 306:219–226Google Scholar
  29. 29.
    Schmidt U, Horster M (1978) Sodium-potassium activated adenosine triphosphatase: Methodology for quantification in microdissected renal tubule segments from freeze-dried and fresh tissue. In: Martinez-Maldonada M (ed) Methods in Pharmacology, Vol 4B. Plenum Press, New York, pp 259–296Google Scholar
  30. 30.
    Schoner W, von Ilberg C, Kramer R, Seubert W (1967) On the mechanism of Na+ and K+ stimulated hydrolysis of adenosine triphosphate. 1. Purification and properties of a Na+ and K+ activated ATPase from ox brain. Eur J Biochem 1:334–343Google Scholar
  31. 31.
    Schultz SG (1981) Homocellular regulatory mechanisms in sodium-transporting epithelia: Avoidance of extinction by “flush-through”. Am J Physiol 241:F579-F590Google Scholar
  32. 32.
    Schwartz GJ, Lin JT, Kinne R (1983) A kinetic assay for Na−K-ATPase activity in isolated renal proximal tubules. Anal Biochem 129:210–215Google Scholar
  33. 33.
    Segal J, Schwartz H, Gordon A (1977) The effect of triiodothyronine on 2-deoxy-d-glucose uptake in cultured chick embryo heart cells. Endocrinology 101:143–149Google Scholar
  34. 34.
    Segal J, Ingbar SH (1982) Specific binding sites for triiodothyronine in the plasma membrane of rat thymocytes. Correlation with biochemical responses. J Clin Invest 70:919–926Google Scholar
  35. 35.
    Smith P, Frizzel R (1984) Chloride secretion by canine tracheal epithelium. VI. Basolateral membrane permeability parallels secretion rate. J Membr Biol 77:187–199Google Scholar
  36. 36.
    Somjen D, Ismail-Beigi, Edelman IS (1981) Nuclear binding of T3 and effects onQO2 Na−K-ATPase and α-GPDH in liver and kidney. Am J Physiol 240: (Endocrinol Metab) E146-E154Google Scholar
  37. 37.
    Windhager EE, Giebisch G (1961) Comparison of short circuit current and net water movement in single perfused proximal tubules of rat kidneys. Nature 191:1205–1207Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • Giovambattista Capasso
    • 1
  • J. -T. Lin
    • 1
  • Natale G. De Santo
    • 2
  • Rolf Kinne
    • 1
  1. 1.Department of Physiology and BiophysicsAlbert Einstein College of MedicineBronxUSA
  2. 2.First Faculty of MedicineUniversity of NaplesNaplesItaly

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