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. 1996 Jan 1;97(1):263–267. doi: 10.1172/JCI118401

Na+/myo-inositol transport is regulated by basolateral tonicity in Madin-Darby canine kidney cells.

A Yamauchi 1, T Sugiura 1, T Ito 1, A Miyai 1, M Horio 1, E Imai 1, T Kamada 1
PMCID: PMC507089  PMID: 8550845

Abstract

We investigated the effects of change in basolateral osmolality on Na(+)-dependent myo-inositol uptake in Madin-Darby canine kidney cells to test our hypothesis that the Na+/myo-inositol transporter (SMIT), an osmolyte transporter, is mainly regulated by osmolality on the basolateral surface. A significant osmotic gradient between both sides of the epithelium persisted at least 10 h after basolateral osmolality was increased. [3H]myo-inositol uptake increased in a basolateral osmolality-dependent manner. The magnitude of the increase is comparable to that for making both sides hypertonic. Apical hypertonicity also increased the uptake on the basal side, but the magnitude of the increase was significantly smaller than the basolateral or both sides hypertonicity. Betaine-gamma-amino-n-butyric acid transporter activity, measured by [3H]gamma-amino-n-butyric uptake, showed a pattern similar to SMIT activity in response to basolateral hypertonicity. The most plausible explanation for the polarized effect of hypertonicity is that the basal membrane is much more water permeable than the apical membrane. These results seem to be consistent with the localization and regulation of the SMIT in vivo.

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Selected References

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  1. Bagnasco S., Balaban R., Fales H. M., Yang Y. M., Burg M. Predominant osmotically active organic solutes in rat and rabbit renal medullas. J Biol Chem. 1986 May 5;261(13):5872–5877. [PubMed] [Google Scholar]
  2. Garcia-Perez A., Burg M. B. Renal medullary organic osmolytes. Physiol Rev. 1991 Oct;71(4):1081–1115. doi: 10.1152/physrev.1991.71.4.1081. [DOI] [PubMed] [Google Scholar]
  3. Giocondi M. C., Friedlander G., Le Grimellec C. ADH modulates plasma membrane lipid order of living MDCK cells via a cAMP-dependent process. Am J Physiol. 1990 Jul;259(1 Pt 2):F95–103. doi: 10.1152/ajprenal.1990.259.1.F95. [DOI] [PubMed] [Google Scholar]
  4. Giocondi M. C., Le Grimellec C. Water permeation in Madin-Darby canine kidney cells is modulated by membrane fluidity. Biochim Biophys Acta. 1991 May 7;1064(2):315–320. doi: 10.1016/0005-2736(91)90317-2. [DOI] [PubMed] [Google Scholar]
  5. Gullans S. R., Verbalis J. G. Control of brain volume during hyperosmolar and hypoosmolar conditions. Annu Rev Med. 1993;44:289–301. doi: 10.1146/annurev.me.44.020193.001445. [DOI] [PubMed] [Google Scholar]
  6. Hebert S. C., Andreoli T. E. Water permeability of biological membranes. Lessons from antidiuretic hormone-responsive epithelia. Biochim Biophys Acta. 1982 May 12;650(4):267–280. doi: 10.1016/0304-4157(82)90019-3. [DOI] [PubMed] [Google Scholar]
  7. Hebert S. C. Hypertonic cell volume regulation in mouse thick limbs. I. ADH dependency and nephron heterogeneity. Am J Physiol. 1986 Jun;250(6 Pt 1):C907–C919. doi: 10.1152/ajpcell.1986.250.6.C907. [DOI] [PubMed] [Google Scholar]
  8. Kwon H. M., Yamauchi A., Uchida S., Preston A. S., Garcia-Perez A., Burg M. B., Handler J. S. Cloning of the cDNa for a Na+/myo-inositol cotransporter, a hypertonicity stress protein. J Biol Chem. 1992 Mar 25;267(9):6297–6301. [PubMed] [Google Scholar]
  9. Le Grimellec C., Friedlander G., Giocondi M. C. Asymmetry of plasma membrane lipid order in Madin-Darby Canine Kidney cells. Am J Physiol. 1988 Jul;255(1 Pt 2):F22–F32. doi: 10.1152/ajprenal.1988.255.1.F22. [DOI] [PubMed] [Google Scholar]
  10. Misfeldt D. S., Hamamoto S. T., Pitelka D. R. Transepithelial transport in cell culture. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1212–1216. doi: 10.1073/pnas.73.4.1212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Miyai A., Yamauchi A., Nakanishi T., Sugita M., Takamitsu Y., Yokoyama K., Itoh T., Andou A., Kamada T., Ueda N. Na+/myo-inositol cotransport is regulated by tonicity in cultured rat mesangial cells. Kidney Int. 1995 Feb;47(2):473–480. doi: 10.1038/ki.1995.60. [DOI] [PubMed] [Google Scholar]
  12. Nakanishi T., Turner R. J., Burg M. B. Osmoregulation of betaine transport in mammalian renal medullary cells. Am J Physiol. 1990 Apr;258(4 Pt 2):F1061–F1067. doi: 10.1152/ajprenal.1990.258.4.F1061. [DOI] [PubMed] [Google Scholar]
  13. Nakanishi T., Turner R. J., Burg M. B. Osmoregulatory changes in myo-inositol transport by renal cells. Proc Natl Acad Sci U S A. 1989 Aug;86(15):6002–6006. doi: 10.1073/pnas.86.15.6002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Persson B. E., Sakai T., Marsh D. J. Juxtaglomerular interstitial hypertonicity in Amphiuma: tubular origin-TGF signal. Am J Physiol. 1988 Mar;254(3 Pt 2):F445–F449. doi: 10.1152/ajprenal.1988.254.3.F445. [DOI] [PubMed] [Google Scholar]
  15. Takenaka M., Bagnasco S. M., Preston A. S., Uchida S., Yamauchi A., Kwon H. M., Handler J. S. The canine betaine gamma-amino-n-butyric acid transporter gene: diverse mRNA isoforms are regulated by hypertonicity and are expressed in a tissue-specific manner. Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1072–1076. doi: 10.1073/pnas.92.4.1072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Takenaka M., Preston A. S., Kwon H. M., Handler J. S. The tonicity-sensitive element that mediates increased transcription of the betaine transporter gene in response to hypertonic stress. J Biol Chem. 1994 Nov 25;269(47):29379–29381. [PubMed] [Google Scholar]
  17. Uchida S., Garcia-Perez A., Murphy H., Burg M. Signal for induction of aldose reductase in renal medullary cells by high external NaCl. Am J Physiol. 1989 Mar;256(3 Pt 1):C614–C620. doi: 10.1152/ajpcell.1989.256.3.C614. [DOI] [PubMed] [Google Scholar]
  18. Uchida S., Yamauchi A., Preston A. S., Kwon H. M., Handler J. S. Medium tonicity regulates expression of the Na(+)- and Cl(-)-dependent betaine transporter in Madin-Darby canine kidney cells by increasing transcription of the transporter gene. J Clin Invest. 1993 Apr;91(4):1604–1607. doi: 10.1172/JCI116367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wirthensohn G., Lefrank S., Schmolke M., Guder W. G. Regulation of organic osmolyte concentrations in tubules from rat renal inner medulla. Am J Physiol. 1989 Jan;256(1 Pt 2):F128–F135. doi: 10.1152/ajprenal.1989.256.1.F128. [DOI] [PubMed] [Google Scholar]
  20. Yamauchi A., Kwon H. M., Uchida S., Preston A. S., Handler J. S. Myo-inositol and betaine transporters regulated by tonicity are basolateral in MDCK cells. Am J Physiol. 1991 Jul;261(1 Pt 2):F197–F202. doi: 10.1152/ajprenal.1991.261.1.F197. [DOI] [PubMed] [Google Scholar]
  21. Yamauchi A., Miyai A., Shimada S., Minami Y., Tohyama M., Imai E., Kamada T., Ueda N. Localization and rapid regulation of Na+/myo-inositol cotransporter in rat kidney. J Clin Invest. 1995 Sep;96(3):1195–1201. doi: 10.1172/JCI118151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Yamauchi A., Nakanishi T., Takamitsu Y., Sugita M., Imai E., Noguchi T., Fujiwara Y., Kamada T., Ueda N. In vivo osmoregulation of Na/myo-inositol cotransporter mRNA in rat kidney medulla. J Am Soc Nephrol. 1994 Jul;5(1):62–67. doi: 10.1681/ASN.V5162. [DOI] [PubMed] [Google Scholar]
  23. Yamauchi A., Uchida S., Kwon H. M., Preston A. S., Robey R. B., Garcia-Perez A., Burg M. B., Handler J. S. Cloning of a Na(+)- and Cl(-)-dependent betaine transporter that is regulated by hypertonicity. J Biol Chem. 1992 Jan 5;267(1):649–652. [PubMed] [Google Scholar]
  24. Yamauchi A., Uchida S., Preston A. S., Kwon H. M., Handler J. S. Hypertonicity stimulates transcription of gene for Na(+)-myo-inositol cotransporter in MDCK cells. Am J Physiol. 1993 Jan;264(1 Pt 2):F20–F23. doi: 10.1152/ajprenal.1993.264.1.F20. [DOI] [PubMed] [Google Scholar]
  25. Yancey P. H., Clark M. E., Hand S. C., Bowlus R. D., Somero G. N. Living with water stress: evolution of osmolyte systems. Science. 1982 Sep 24;217(4566):1214–1222. doi: 10.1126/science.7112124. [DOI] [PubMed] [Google Scholar]

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