Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1995 Jan;95(1):195–202. doi: 10.1172/JCI117638

In vitro fluid secretion by epithelium from polycystic kidneys.

J J Grantham 1, M Ye 1, V H Gattone 2nd 1, L P Sullivan 1
PMCID: PMC295404  PMID: 7814614

Abstract

The size of the kidneys in patients with autosomal dominant polycystic kidney disease (ADPKD) is due in large measure to the accumulation of secreted fluid within thin-walled epithelial sacs. We measured the net transepithelial movement of liquid in response to forskolin in isolated, intact cysts excised from the surface of human ADPKD kidneys and in cultured, polarized monolayers of epithelial cells derived from ADPKD cysts. 10 excised cysts bathed symmetrically in control culture medium secreted fluid at a rate of 0.19 +/- 0.03 microliter/cm2 per hour after stimulation with forskolin (10 microM). Ouabain (100 microM) addition to the cavity fluid did not change the rate of fluid secretion of 10 forskolin-treated cysts, but addition of the glycoside to the external bathing medium fluid of nine cysts decreased secretion to -0.004 +/- 0.05 microliter/cm2 per hour. 24 monolayers absorbed fluid (range -0.029 to -0.412 microliter/cm2 per hour); by contrast, fluid was secreted (range 0.074 to 1.242 microliters/cm2 per hour) after stimulation with forskolin (10 microM). Ouabain (0.1 microM) in the basolateral but not in the apical medium inhibited fluid secretion. Forskolin increased the intracellular cyclic AMP content of ADPKD and MDCK monolayers by 236 and 196%, respectively. Six ADPKD monolayers had stable lumen negative transepithelial electrical potential differences (PDte) of -1.4 +/- 0.3 mV, positive short circuit currents (SCC) of 11.9 +/- 2.1 microAmp/cm2 and a tissue resistance (Rte) of 116 +/- 14 ohm.cm2. Forskolin increased SCC to 15.5 +/- 1.9 microAmp/cm2 (P < 0.005) and decreased Rte to 95 +/- 13 ohm.cm2 (P < 0.05); PDte remained stable at -1.4 +/- 0.3 mV. Ouabain (10 microM) had no effect when added to the apical medium, but in the basolateral medium decreased SCC to 1.7 +/- 0.3 microAmp/cm2 and PDte to -0.2 +/- 0.1 mV. We conclude that ADPKD cells in surface cysts have the potential to absorb or to secrete solutes and fluid. cAMP-mediated fluid secretion from the basolateral medium into the lumen of surface ADPKD cysts may be driven by anion transport.

Full text

PDF
195

Images in this article

197Image
on p.197

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Carone F. A., Nakamura S., Caputo M., Bacallao R., Nelson W. J., Kanwar Y. S. Cell polarity in human renal cystic disease. Lab Invest. 1994 May;70(5):648–655. [PubMed] [Google Scholar]
  2. Gardner K. D., Jr, Burnside J. S., Skipper B. J., Swan S. K., Bennett W. M., Connors B. A., Evan A. P. On the probability that kidneys are different in autosomal dominant polycystic disease. Kidney Int. 1992 Nov;42(5):1199–1206. doi: 10.1038/ki.1992.405. [DOI] [PubMed] [Google Scholar]
  3. Gardner K. D., Jr Composition of fluid in twelve cysts of a polycystic kidney. N Engl J Med. 1969 Oct 30;281(18):985–988. doi: 10.1056/NEJM196910302811804. [DOI] [PubMed] [Google Scholar]
  4. Gardner K. D., Jr, Glew R. H., Evan A. P., McAteer J. A., Bernstein J. Why renal cysts grow. Am J Physiol. 1994 Mar;266(3 Pt 2):F353–F359. doi: 10.1152/ajprenal.1994.266.3.F353. [DOI] [PubMed] [Google Scholar]
  5. Grant M. E., Neufeld T. K., Cragoe E. J., Jr, Welling L. W., Grantham J. J. Arginine vasopressin stimulates net fluid secretion in a polarized subculture of cyst-forming MDCK cells. J Am Soc Nephrol. 1991 Aug;2(2):219–227. doi: 10.1681/ASN.V22219. [DOI] [PubMed] [Google Scholar]
  6. Grantham J. J. 1992 Homer Smith Award. Fluid secretion, cellular proliferation, and the pathogenesis of renal epithelial cysts. J Am Soc Nephrol. 1993 Jun;3(12):1841–1857. doi: 10.1681/ASN.V3121841. [DOI] [PubMed] [Google Scholar]
  7. Grantham J. J., Geiser J. L., Evan A. P. Cyst formation and growth in autosomal dominant polycystic kidney disease. Kidney Int. 1987 May;31(5):1145–1152. doi: 10.1038/ki.1987.121. [DOI] [PubMed] [Google Scholar]
  8. Grantham J. J., Uchic M., Cragoe E. J., Jr, Kornhaus J., Grantham J. A., Donoso V., Mangoo-Karim R., Evan A., McAteer J. Chemical modification of cell proliferation and fluid secretion in renal cysts. Kidney Int. 1989 Jun;35(6):1379–1389. doi: 10.1038/ki.1989.137. [DOI] [PubMed] [Google Scholar]
  9. Hammerton R. W., Krzeminski K. A., Mays R. W., Ryan T. A., Wollner D. A., Nelson W. J. Mechanism for regulating cell surface distribution of Na+,K(+)-ATPase in polarized epithelial cells. Science. 1991 Nov 8;254(5033):847–850. doi: 10.1126/science.1658934. [DOI] [PubMed] [Google Scholar]
  10. Huseman R., Grady A., Welling D., Grantham J. Macropuncture study of polycystic disease in adult human kidneys. Kidney Int. 1980 Sep;18(3):375–385. doi: 10.1038/ki.1980.148. [DOI] [PubMed] [Google Scholar]
  11. Mangoo-Karim R., Uchic M. E., Grant M., Shumate W. A., Calvet J. P., Park C. H., Grantham J. J. Renal epithelial fluid secretion and cyst growth: the role of cyclic AMP. FASEB J. 1989 Dec;3(14):2629–2632. doi: 10.1096/fasebj.3.14.2480260. [DOI] [PubMed] [Google Scholar]
  12. Mangoo-Karim R., Uchic M., Lechene C., Grantham J. J. Renal epithelial cyst formation and enlargement in vitro: dependence on cAMP. Proc Natl Acad Sci U S A. 1989 Aug;86(15):6007–6011. doi: 10.1073/pnas.86.15.6007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McCabe R. D., Smith P. L., Sullivan L. P. Ion transport by rabbit descending colon: mechanisms of transepithelial potassium transport. Am J Physiol. 1984 May;246(5 Pt 1):G594–G602. doi: 10.1152/ajpgi.1984.246.5.G594. [DOI] [PubMed] [Google Scholar]
  14. Perrone R. D. In vitro function of cyst epithelium from human polycystic kidney. J Clin Invest. 1985 Oct;76(4):1688–1691. doi: 10.1172/JCI112155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Perrone R. D., McLaughlin M. L. Cyst function in polycystic kidney disease: nongradient cysts. Clin Nephrol. 1989 Sep;32(3):113–118. [PubMed] [Google Scholar]
  16. Smith J. J., Welsh M. J. Fluid and electrolyte transport by cultured human airway epithelia. J Clin Invest. 1993 Apr;91(4):1590–1597. doi: 10.1172/JCI116365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sullivan L. P., Tucker J. M., Scherbenske M. J. Effect of furosemide on sodium transport and metabolism in toad bladder. Am J Physiol. 1971 May;220(5):1316–1324. doi: 10.1152/ajplegacy.1971.220.5.1316. [DOI] [PubMed] [Google Scholar]
  18. Sullivan L. P., Wallace D. P., Grantham J. J. Coupling of cell volume and membrane potential changes to fluid secretion in a model of renal cysts. Kidney Int. 1994 May;45(5):1369–1380. doi: 10.1038/ki.1994.179. [DOI] [PubMed] [Google Scholar]
  19. Takahashi H., Calvet J. P., Dittemore-Hoover D., Yoshida K., Grantham J. J., Gattone V. H., 2nd A hereditary model of slowly progressive polycystic kidney disease in the mouse. J Am Soc Nephrol. 1991 Jan;1(7):980–989. doi: 10.1681/ASN.V17980. [DOI] [PubMed] [Google Scholar]
  20. Welsh M. J., Smith P. L., Fromm M., Frizzell R. A. Crypts are the site of intestinal fluid and electrolyte secretion. Science. 1982 Dec 17;218(4578):1219–1221. doi: 10.1126/science.6293054. [DOI] [PubMed] [Google Scholar]
  21. Wilson P. D., Sherwood A. C., Palla K., Du J., Watson R., Norman J. T. Reversed polarity of Na(+) -K(+) -ATPase: mislocation to apical plasma membranes in polycystic kidney disease epithelia. Am J Physiol. 1991 Mar;260(3 Pt 2):F420–F430. doi: 10.1152/ajprenal.1991.260.3.F420. [DOI] [PubMed] [Google Scholar]
  22. Ye M., Grantham J. J. The secretion of fluid by renal cysts from patients with autosomal dominant polycystic kidney disease. N Engl J Med. 1993 Jul 29;329(5):310–313. doi: 10.1056/NEJM199307293290503. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES