Skip to main content
Log in

Manganese transport by caco-2 cells

  • Original Articles
  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

The uptake and transport kinetics of manganese (Mn) were investigated in the human intestinal Caco-2 cell line both from the absorption side (apical to basolateral) and from the exsorption side (basolateral to apical). With regard to the former, transport versus time revealed (as uptake) a biphasic pattern with an initial transient phase followed by steady-state conditions. Uptake versus Mn concentrations showed saturation-type kinetics with a 100% increase of Mn binding capacity when measurements were made from 0.5 to 2 h of incubation. The transport characteristics in steady-state conditions exhibited two components, saturable (Vmax = 3.70 ± 0.07 nmol/cm2/h, Km = 32.2 ± 3.4 μM) and nonsaturable (slope = [1.4 ± 0.2] x 10-6 cm-2/h) usually presumed to reflect transcellular (carrier mediated) and paracellular (diffusional) pathways, respectively. Mn fluxes were decreased by calcium and calcium antagonists, almost 100% inhibited at 4°C, and affected by quinacrine and ouabain. The inhibition of ATP synthesis was apparently ineffective. From the exsorption side, the Mn fluxes, without a transient period, had an approx 20-fold smaller rate than in the absorptive direction and showed mainly a nonsaturable route (slope = [0.6 ± 0.1] x 10-6 cm-2/h). The mechanisms participating in the Mn movements through the monolayer are discussed and proposed to be in common, at least partly, with other divalent cations such as calcium, zinc, or iron.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. L. S. Hurley and C. L. Keen, Manganese, inTrace Elements in Human and Animal Nutrition, W. Mertz, ed., Academic, New York, Vol. 1, pp. 185–192 (1987).

    Google Scholar 

  2. R. G. Banta and W. R. Markesbery, Elevated manganese levels associated with dementia and extrapyramidal signs,Neurology 213, 27–32 (1977).

    Google Scholar 

  3. X. G. Kondakis, N. Makris, M. Leotsinidis, M. Prinou, and T. Papapetropoulos, Possible health effects of high manganese concentration in drinking water,Arch. Environ. Health 44, 175–178 (1989).

    Article  PubMed  CAS  Google Scholar 

  4. J. A. Garcia-Aranda, R. A. Wapnir, and F. Lifshtiz, In vivo intestinal absorption of manganese in the rat,J. Nutr. 113, 2601–2607 (1983).

    PubMed  CAS  Google Scholar 

  5. D. Y. Lee and P. E. Johnson, Factors affecting absorption and excretion of54Mn in rats,J. Nutr. 118, 1509–1516 (1988).

    PubMed  CAS  Google Scholar 

  6. G. Testolin, S. Ciappellano, A. Alberio, F. Piccinini, L. Paracchini, and A. Jotti, Intestinal absorption of manganese: an in vitro study,Ann. Nutr. Metab. 37, 289–294 (1993).

    Article  PubMed  CAS  Google Scholar 

  7. M. Kato, Distribution and excretion of radiomanganese administered to the mouse,Quart, J. Exp. Physiol. 48, 355–369 (1963).

    CAS  Google Scholar 

  8. M. Cikrt, Enterohepatic circulation of64Cu,54Mn and203Hg in rats,Arch. Toxicol. 31, 51–59 (1973).

    Article  CAS  Google Scholar 

  9. R. M. Leach and M. S. Liburn, Manganese metabolism and its function,World Rev. Nutr. Diet 32, 123–134 (1978).

    PubMed  CAS  Google Scholar 

  10. B. Lönnerdal, C. L. Keen, J. G. Bell, and B. Sandström, Manganese uptake and retention, inNutritional Bioavailability of Manganese, C. Kies, ed., American Chemical Society, Washington, DC, pp. 9–20 (1987).

    Google Scholar 

  11. A. B. R. Thomson, D. Olatunbosun, and L. S. Valberg, Interrelation of intestinal transport system for manganese and iron,J. Lab. Clin. Med. 78, 642–655 (1971).

    PubMed  CAS  Google Scholar 

  12. A. B. R. Thomson, and L. S. Valberg, Kinetics of intestinal iron absorption in the rat: effect of cobalt,Am. J. Physiol. 220, 1080–1085 (1971).

    PubMed  CAS  Google Scholar 

  13. T. A. Lutz, A. Schroff, and E. Scharrer, Effect of calcium and sugars on intestinal manganese absorption,Biol. Trace Element Res. 39, 221–227 (1993).

    CAS  Google Scholar 

  14. I. J. Hidalgo, T. J. Raub, and R. T. Borchardt, Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability,Gastroenterology 96, 736–749 (1989).

    PubMed  CAS  Google Scholar 

  15. P. Artursson, Epithelial transport of drugs in cell culture, a model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells,J. Pharm. Sci. 79, 476–782 (1990).

    Article  PubMed  CAS  Google Scholar 

  16. A. R. Hilgers, R. A. Conradi, and P. S. Burton, Caco-2 cell monolayers as a model for drug transport for study transport across the intestinal mucosa,Pharm. Res. 7, 902–910 (1990).

    Article  PubMed  CAS  Google Scholar 

  17. E. Walter and T. Kissel, Heterogeneity in the human intestinal cell line Caco-2 leads to differences in transepithelial transport,J. Pharm. Sci. 3, 215–230 (1995).

    Article  CAS  Google Scholar 

  18. D. Pansu, C. Bellaton, and F. Bronner, Effect of Ca intake on saturable and non saturable components of duodenal Ca transport,Am. J. Physiol. 240, G32-G37 (1981).

    PubMed  CAS  Google Scholar 

  19. D. Triglia, S. S. Braa, C. Yonan, and G. K. Naughton, In vitro toxicity of various classes of test agents using the neutral red assay on a human three-dimensional physiologic skin model,In Vitro Cell. Dev. Biol. 27A, 239–244 (1991).

    Article  PubMed  CAS  Google Scholar 

  20. B. Gumbiner, Structure, biochemistry and assembly of epithelial tight junctions,Am. J. Physiol. 253, C749-C758 (1987).

    PubMed  CAS  Google Scholar 

  21. D. R. Pitelka, B. N. Taggart, and S. T. Hamamoto, Effect of extracellular calcium depletion on membrane topography and occluding junctions of mammary epithelial cell in culture,J. Cell Biol. 96, 613–624 (1983).

    Article  PubMed  CAS  Google Scholar 

  22. P. L. Nicklin, W. J. Irwin, I. F. Hassan, and M. Mackay, Development of a minimum calcium Caco-2 monolayer model: calcium and magnesium ions retard the transport of pamidronate,Int. J. Pharm. 123, 187–197 (1995).

    Article  CAS  Google Scholar 

  23. M. W. Walling, Intestinal calcium and phosphate transport: differential responses to vitamin D3 metabolites,Am. J. Physiol. 233, 488–494 (1977).

    Google Scholar 

  24. I. Nemere, U. Leathers, and A. W. Norman, 1,25 dihydroxyvitamin D2 mediated intestinal calcium transport,J. Biol. Chem. 261, 16106–16114 (1986).

    PubMed  CAS  Google Scholar 

  25. J. C. Fleet, A. J. Turnbull, M. Bourcier, and R. J. Wood, Vitamin-D sensitive and quinacrine-sensitive zinc transport in human intestinal cell line Caco-2,Am. J. Physiol. 264, G1037-G1045 (1993).

    PubMed  CAS  Google Scholar 

  26. X. A. Hernandez, G. M. Nichols, and J. Glass, Caco-2 cell line: a system for studying intestinal transport across epithelia cell monolayer,Biochim. Biophys. Acta 1070, 205–208 (1991).

    Article  Google Scholar 

  27. T. Galeotti, G. Palombini, and D. V. van Rossum, Manganese content and high-affinity transport in liver and hepatoma,Arch. Biochem. Biophys. 322, 453–459 (1995).

    Article  PubMed  CAS  Google Scholar 

  28. M. Aschner and M. Gannon, Manganese (Mn) transport across the rat blood-brain barrier: saturable and transferrin-dependent transport mechanisms,Brain Res. Bull. 33, 345–349 (1994).

    Article  PubMed  CAS  Google Scholar 

  29. F. Bronner, D. Pansu, and W. D Stein, An analysis of intestinal calcium transport across the rat intestine,Am. J. Physiol. 250, G561-G569 (1986).

    PubMed  CAS  Google Scholar 

  30. L. Davidsson, A. Cederblad, B. Lnnerdal, and B. Sandstrm, The effect of individual dietary components on manganese absorption in humans,Am. J. Clin. Nutr. 54, 1065–1070 (1991).

    PubMed  CAS  Google Scholar 

  31. A. Miller, S. T. Li, and F. Bronner, Characterization of calcium binding to brush-border membranes from rat duodenum,Biochem. J. 208, 773–781 (1982).

    PubMed  CAS  Google Scholar 

  32. N. Surendran, L. D. Nguyen, A. R. Giuliano, and J. Blanchard, Mechanisms of acylcarnitine-mediated enhancement of calcium transport in the Caco-2 cell monolayer model,J. Pharm. Sci. 84, 269–274 (1995).

    Article  PubMed  CAS  Google Scholar 

  33. K. Thorstensen and I. Romslo, Uptake of iron from transferrin by isolated rat hepatocytes,J. Biol. Chem. 263, 8844–8850 (1988).

    PubMed  CAS  Google Scholar 

  34. W. Breuer, S. Epsztejn, P. Millgram, and I. Z. Cabantchik, Transport of iron and other transient metals into cells as revealed by a fluorescent probe,Am. J. Physiol. 268, C1354-C1361 (1995).

    PubMed  CAS  Google Scholar 

  35. R. D. Raffaniello, S. Y. Lee, S. Teichberg, and R. A. Wapnir, Distinct mechanisms of zinc uptake at the apical and basolateral membranes of Caco-2 cells,J. Cell Physiol. 152, 356–361 (1992).

    Article  PubMed  CAS  Google Scholar 

  36. W. E. J. M. Ghijjen, M. D. De Jong, and C. H. Van Os, Kinetic properties of Na+/Ca2+ exchange in basolateral plasma membranes of rat small intestine,Biochim. Biophys. Acta 730, 85–94 (1983).

    Article  Google Scholar 

  37. A. L. Salzman, M. J. Menconi, N. Unno, R. M. Ezzell, D. M. Casey, P. K. Gonzalez, et al., Nitric oxide dilate tight junctions and deplete ATP in cultured Caco-2BBe intestinal epithelial monolayer,Am. J. Physiol. 268, G361-G373 (1995).

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leblondel, G., Allain, P. Manganese transport by caco-2 cells. Biol Trace Elem Res 67, 13–28 (1999). https://doi.org/10.1007/BF02784271

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02784271

Index entries

Navigation