The Journal of Physiological Sciences

, Volume 69, Issue 2, pp 245–251 | Cite as

Exhaustive exercise decreases renal organic anion transporter 3 function

  • Tipwadee Bunprajun
  • Chaowalit Yuajit
  • Rattikarn Noitem
  • Varanuj ChatsudthipongEmail author
Original Paper


This study aimed to investigate the effects of various types of exercise on organic anion transporter 3 (Oat3) function, a major transporter that plays a role in the secretion of a variety of drugs and endogenous compounds. Male Wistar rats were randomly allocated to non-exercise, exhaustive, acute and training exercise groups. The function of Oat3 was assessed by the uptake of [3H]-estrone sulfate ([3H]-ES) into rat renal cortical slices. Acute and training exercises had no effect on [3H]-ES uptake whereas a marked reduction in [3H]-ES uptake occurred immediately after exhaustive exercise. However, the reduction in Oat3 function was gradually recovered at 6 and 24 h after the exercise session. Importantly, the impairment of Oat3 function was associated with a decrease in renal Oat3 protein expression. Our results indicate that exhaustive exercise produces a significant impact on renal organic anion transport function, which in turn could alter the plasma level of drugs and compounds in the body.


Exercise Exhaustive exercise Training Renal secretory process Organic anion transporter 3 



The proof reading of this manuscript was supported by the Editorial Office, Faculty of Graduate Studies, Mahidol University.

Author contributions

TB, CY, and RN performed biochemical assays, uptake study, and animal experiment. TB analyzed data, interpreted results and wrote the manuscript. TB and VC designed the project. VC supervised the project and revised the manuscript.


This study was supported by the Thailand Research Fund (TRG5780104) and Mahidol University (TM 42/2557).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures in this study were conducted in accordance with the guidelines of the National Laboratory Animal Center of Thailand. The protocol was approved by the Animal Care and Use Committee of the Faculty of Science, Mahidol University, Thailand (MUSC57-003-298).


  1. 1.
    American College of Sports Medicine (2014) ACSM’s guidelines for exercise testing and prescription. Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  2. 2.
    American College of Sports Medicine (2012) ACSM’s advanced exercise physiology. Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  3. 3.
    Wong DT, Lee KJ, Yoo SJ, Tomlinson G, Grosse-Wortmann L (2014) Changes in systemic and pulmonary blood flow distribution in normal adult volunteers in response to posture and exercise: a phase contrast magnetic resonance imaging study. J Physiol Sci 64:105–112CrossRefGoogle Scholar
  4. 4.
    Lenz TL (2011) The effects of high physical activity on pharmacokinetic drug interactions. Expert Opin Drug Metab Toxicol 7:257–266CrossRefGoogle Scholar
  5. 5.
    Lenz TL, Lenz NJ, Faulkner MA (2004) Potential interactions between exercise and drug therapy. Sports Med 34:293–306CrossRefGoogle Scholar
  6. 6.
    Somani SM, Kamimori GH (1996) Pharmacology in exercise and sports. CRC Press, Boca RatonGoogle Scholar
  7. 7.
    Ylitalo P, Hinkka H (1985) Effect of exercise on plasma levels and urinary excretion of sulphadimidine and procainamide. Int J Clin Pharmacol Ther Toxicol 23:548–553Google Scholar
  8. 8.
    Ylitalo P, Hinkka H, Neuvonen PJ (1977) Effect of exercise on the serum level and urinary excretion of tetracycline, doxycycline and sulphamethizole. Eur J Clin Pharmacol 12:367–373CrossRefGoogle Scholar
  9. 9.
    Morrissey KM, Stocker SL, Wittwer MB, Xu L, Giacomini KM (2013) Renal transporters in drug development. Annu Rev Pharmacol Toxicol 53:503–529CrossRefGoogle Scholar
  10. 10.
    Wright SH, Dantzler WH (2004) Molecular and cellular physiology of renal organic cation and anion transport. Physiol Rev 84:987–1049CrossRefGoogle Scholar
  11. 11.
    Pritchard JB, Miller DS (1993) Mechanisms mediating renal secretion of organic anions and cations. Physiol Rev 73:765–796CrossRefGoogle Scholar
  12. 12.
    Masereeuw R, Russel FG (2010) Therapeutic implications of renal anionic drug transporters. Pharmacol Ther 126:200–216CrossRefGoogle Scholar
  13. 13.
    Motohashi H, Sakurai Y, Saito H, Masuda S, Urakami Y, Goto M, Fukatsu A, Ogawa O, Inui K (2002) Gene expression levels and immunolocalization of organic ion transporters in the human kidney. J Am Soc Nephrol 13:866–874Google Scholar
  14. 14.
    Kobayashi Y, Hirokawa N, Ohshiro N, Sekine T, Sasaki T, Tokuyama S, Endou H, Yamamoto T (2002) Differential gene expression of organic anion transporters in male and female rats. Biochem Biophys Res Commun 290:482–487CrossRefGoogle Scholar
  15. 15.
    Sakurai Y, Motohashi H, Ueo H, Masuda S, Saito H, Okuda M, Mori N, Matsuura M, Doi T, Fukatsu A, Ogawa O, Inui K (2004) Expression levels of renal organic anion transporters (OATs) and their correlation with anionic drug excretion in patients with renal diseases. Pharm Res 21:61–67CrossRefGoogle Scholar
  16. 16.
    Villar SR, Brandoni A, Anzai N, Endou H, Torres AM (2005) Altered expression of rat renal cortical OAT1 and OAT3 in response to bilateral ureteral obstruction. Kidney Int 68:2704–2713CrossRefGoogle Scholar
  17. 17.
    Hao Z, Pan SS, Shen YJ, Ge J (2014) Exercise preconditioning-induced late phase of cardioprotection against exhaustive exercise: possible role of protein kinase C delta. J Physiol Sci 64:333–345CrossRefGoogle Scholar
  18. 18.
    Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H (2001) Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol 59:1277–1286CrossRefGoogle Scholar
  19. 19.
    Feng B, Dresser MJ, Shu Y, Johns SJ, Giacomini KM (2001) Arginine 454 and lysine 370 are essential for the anion specificity of the organic anion transporter, rOAT3. Biochemistry 40:5511–5520CrossRefGoogle Scholar
  20. 20.
    Eaton DC, Pooler JP (2009) Vander’s renal physiology. McGraw-Hill Education, New YorkGoogle Scholar
  21. 21.
    Perrone RD, Madias NE, Levey AS (1992) Serum creatinine as an index of renal function: new insights into old concepts. Clin Chem 38:1933–1953Google Scholar
  22. 22.
    Popov DV, Bachinin AV, Lysenko EA, Miller TF, Vinogradova OL (2014) Exercise-induced expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha isoforms in skeletal muscle of endurance-trained males. J Physiol Sci 64:317–323CrossRefGoogle Scholar
  23. 23.
    Mazzeo RS, Brooks GA, Horvath SM (1984) Effects of age on metabolic responses to endurance training in rats. J Appl Physiol Respir Environ Exerc Physiol 57:1369–1374Google Scholar
  24. 24.
    Niu AJ, Wu JM, Yu DH, Wang R (2008) Protective effect of Lycium barbarum polysaccharides on oxidative damage in skeletal muscle of exhaustive exercise rats. Int J Biol Macromol 42:447–449CrossRefGoogle Scholar
  25. 25.
    Oh MS (1993) Does serum creatinine rise faster in rhabdomyolysis? Nephron 63:255–257CrossRefGoogle Scholar
  26. 26.
    Vallon V, Eraly SA, Rao SR, Gerasimova M, Rose M, Nagle M, Anzai N, Smith T, Sharma K, Nigam SK, Rieg T (2012) A role for the organic anion transporter OAT3 in renal creatinine secretion in mice. Am J Physiol Renal Physiol 302:F1293–F1299CrossRefPubMedCentralGoogle Scholar
  27. 27.
    Schneider R, Sauvant C, Betz B, Otremba M, Fischer D, Holzinger H, Wanner C, Galle J, Gekle M (2007) Downregulation of organic anion transporters OAT1 and OAT3 correlates with impaired secretion of para-aminohippurate after ischemic acute renal failure in rats. Am J Physiol Renal Physiol 292:F1599–F1605CrossRefGoogle Scholar
  28. 28.
    Soodvilai S, Chatsudthipong V, Evans KK, Wright SH, Dantzler WH (2004) Acute regulation of OAT3-mediated estrone sulfate transport in isolated rabbit renal proximal tubules. Am J Physiol Renal Physiol 287:F1021–F1029CrossRefGoogle Scholar
  29. 29.
    Brooks GA, Fahey TD, Baldwin KM (2005) Exercise physiology: human bioenergetics and its applications. McGraw-Hill Education, BostonGoogle Scholar
  30. 30.
    Lehmann M, Keul J, Huber G, Da Prada M (1981) Plasma catecholamines in trained and untrained volunteers during graduated exercise. Int J Sports Med 2:143–147CrossRefGoogle Scholar
  31. 31.
    Bloom SR, Johnson RH, Park DM, Rennie MJ, Sulaiman WR (1976) Differences in the metabolic and hormonal response to exercise between racing cyclists and untrained individuals. J Physiol 258:1–18CrossRefPubMedCentralGoogle Scholar
  32. 32.
    Galbo H, Holst JJ, Christensen NJ (1975) Glucagon and plasma catecholamine responses to graded and prolonged exercise in man. J Appl Physiol 38:70–76CrossRefGoogle Scholar
  33. 33.
    Meredith IT, Friberg P, Jennings GL, Dewar EM, Fazio VA, Lambert GW, Esler MD (1991) Exercise training lowers resting renal but not cardiac sympathetic activity in humans. Hypertension 18:575–582CrossRefGoogle Scholar
  34. 34.
    Xu D, Wang H, You G (2016) An essential role of Nedd4-2 in the ubiquitination, expression, and function of organic anion transporter-3. Mol Pharm 13:621–630CrossRefGoogle Scholar

Copyright information

© The Physiological Society of Japan and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  • Tipwadee Bunprajun
    • 1
  • Chaowalit Yuajit
    • 2
  • Rattikarn Noitem
    • 3
  • Varanuj Chatsudthipong
    • 3
    • 4
    Email author
  1. 1.Faculty of Physical TherapyMahidol UniversitySalayaThailand
  2. 2.College of Medicine and Public HealthUbon Ratchathani UniversityUbon RatchathaniThailand
  3. 3.Department of Physiology, Faculty of ScienceMahidol UniversityBangkokThailand
  4. 4.Research Center of Transport Protein for Medical Innovation, Faculty of ScienceMahidol UniversityBangkokThailand

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