Skip to main content
Log in

Influence of rat strain on P-glycoprotein expression in cultured hepatocytes

Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

The amount and activity of the multi-drug transport P-glycoprotein (Pgp) have been measured in cultured hepatocytes derived from different rat strains. A marked increase in Pgp, as revealed by Western blotting, occurred 48 h after seeding in hepatocytes from Sprague-Dawley, Wistar and Fischer 344 rats, the last showing the highest value. The addition of dexamethasone (DEX) to culture medium delayed Pgp overexpression in all the strains, proportionally to the protein amount in the absence of hormone. The R-123 functional test for Pgp showed that Fischer 344 hepatocytes had the lowest ability to extrude the fluorescent dye as compared with Sprague-Dawley or Wistar rats. These results suggest that the Fischer 344 rat is more prone than other strains to culture stressing conditions, leading to an overexpression of Pgp that is not necessarily functional.

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.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

DEX:

dexamethasone

FCS:

fetal calf serum

HRP:

horseradish peroxide

Pgp:

P-glycoprotein

References

  • Carr BI. Spontaneous development of pleiotropic drug resistance in rat hepatocytes with time in culture. Proc AACR. 1988;29:291.

    Google Scholar 

  • Chieli E, Santoni Rugiu E, Cervelli F, Paolicchi A, Tongiani R. Assessment of P-glycoprotein dependent drug transport in isolated rat hepatocytes using rhodamine-123. Cell Biol Toxicol. 1993;9:235–41.

    Google Scholar 

  • Chieli E, Santoni Rugiu E, Cervelli F et al. Differential modulation of P-glycoprotein expression by dexamethasone and 3-methylcholanthrene in rat hepatocyte primary cultures. Carcinogenesis. 1994;15:335–41.

    Google Scholar 

  • Endicott JA, Ling V. The biochemistry of P-glycoprotein-mediated multidrug resistance. Annu Rev Biochem. 1989;58:137–71.

    Google Scholar 

  • Farber E. Hyperplastic liver nodules. Methods Cancer Res. 1973;7:345–71.

    Google Scholar 

  • Fardel O, Loyer P, Morel F, Ratanasavanh D, Guillouzo A. Modulation of multidrug resistance gene expression in rat hepatocytes maintained under various culture conditions. Biochem Pharmacol. 1992a;44:2259–62.

    Google Scholar 

  • Fardel O, Ratanasavanh D, Loyer P, Ketterer B, Guillouzo A. Overexpression of the multidrug resistance gene product in adult rat hepatocytes during primary culture. Eur J Biochem. 1992b;205:847–52.

    Google Scholar 

  • Fardel O, Lecureur V, Guillouzo A. Regulation by dexamethasone of P-glycoprotein expression in cultured rat hepatocytes. FEBS Lett. 1993a;327:189–93.

    Google Scholar 

  • Fardel O, Morel F, Guillouzo A. P-glycoprotein expression in human, mouse, hamster and rat hepatocytes in primary culture. Carcinogenesis. 1993b;14:781–3.

    Google Scholar 

  • Gant TW, Silverman JA, Bisgaard HC, Burt RK, Marino PA, Thorgeirsson SS. Regulation of 2-acetylaminofluorene- and 3-methylcholanthrene-mediated induction of multidrug resistance and cytochrome P-450IA gene family expression in primary hepatocyte cultures and rat liver. Mol Carcinogen. 1991;4:499–509.

    Google Scholar 

  • Georges E, Tsuruo T, Ling V. Topology of P-glycoprotein as determined by epitope mapping of MRK-16 monoclonal antibody. J Biol Chem. 1993;268:1792–8.

    Google Scholar 

  • Gonzalez FJ. The molecular biology of cytochrome P450s. Pharmacol Rev. 1989;40:243–88.

    Google Scholar 

  • Herzog CE, Trepel JB, Mickley LA, Bates SE, Fojo AT. Various methods of analysis of mdr-1/P-glycoprotein in human colon cancer cell lines. J Natl Cancer Inst. 1992;84:711–6.

    Google Scholar 

  • Ishikawa T. The ATP-dependent glutathione S-conjugate export pump. TIBS. 1992;17:463–8.

    Google Scholar 

  • Kamimoto Y, Gatmaitan Z, Hsu J, Arias IM. The function of Gp170, the multidrug resistance gene product, in rat liver canalicular membrane vescicles. J Biol Chem. 1989;264:11639–98.

    Google Scholar 

  • Pastan I, Gottesman MM. Multidrug resistance. Annu Rev Med. 1991;42:277–86.

    Google Scholar 

  • Peterson GL. A simplification of the protein assay method of Lowry. Anal Biochem. 1977;83:346–56.

    Google Scholar 

  • Schuetz JD, Schuetz EG. Extracellular matrix regulation of multidrug resistance in primary monolayer cultures of adult rat hepatocytes. Cell Growth Differ. 1993;4:31–40.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chieli, E., Romiti, N., Cervelli, F. et al. Influence of rat strain on P-glycoprotein expression in cultured hepatocytes. Cell Biol Toxicol 10, 163–166 (1994). https://doi.org/10.1007/BF00757559

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00757559

Keywords

Navigation