Skip to main content
Log in

γ-Aminobutyric Acid B Receptor Improves Carbon Tetrachloride-Induced Liver Fibrosis in Rats

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

It was well known that angiotension II can inhibit hepatic stellate cell activation. The GABAB receptor was upregulated when the hepatic stellate cell line was stimulated by angiotension II in our previous study. But the role of the GABAB receptor in liver fibrosis has never been reported.

Aim

In the present study, we investigated the effects of this receptor on carbon tetrachloride-induced liver fibrosis in rats.

Methods

The rats were divided into four groups including GABAB receptor agonist, antangonist, model and control group. α-smooth muscle actin (α-SMA) and GABAB receptor expression levels were detected by immunohistochemistry and real-time polymerase chain reaction. Liver function tests were performed once blood samples was taken; Western blot analysis was used to detect protein expression level of α-SMA and TGF-β1.

Results

We found baclofen ameliorated the CCl4-induced rats’s liver fibrosis. The highest liver enzymes and α-SMA protein levels were found in the CGP35348 group.

Conclusion

The GABAB receptor may have a protective role in the liver.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Friedman SL. Seminars in medicine of the Beth Israel Hospital, Boston. The cellular basis of hepatic fibrosis. Mechanisms and treatment strategies. N Engl J Med. 1993;328:1828–1835.

    Article  PubMed  CAS  Google Scholar 

  2. Abdel-Aziz G, Lebeau G, Rescan PY, et al. Reversibility of hepatic fibrosis in experimentally induced cholestasis in rat. Am J Pathol. 1990;137:1333–1342.

    PubMed  CAS  Google Scholar 

  3. Dufour JF, DeLellis R, Kaplan MM. Regression of hepatic fibrosis in hepatitis C with long-term interferon treatment. Dig Dis Sci. 1998;43:2573–2576.

    Article  PubMed  CAS  Google Scholar 

  4. Farci P, Roskams T, Chessa L, et al. Long-term benefit of interferon alpha therapy of chronic hepatitis D: regression of advanced hepatic fibrosis. Gastroenterology. 2004;126:1740–1749.

    Article  PubMed  CAS  Google Scholar 

  5. Rojkind M, Dunn MA. Hepatic fibrosis. Gastroenterology. 1979;76:849–863.

    PubMed  CAS  Google Scholar 

  6. Iredale JP, Benyon RC, Pickering J, et al. Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors. J Clin Invest. 1998;102:538–549.

    Article  PubMed  CAS  Google Scholar 

  7. Lewis M, Howdle PD. The neurology of liver failure. QJM. 2003;96:623–633.

    Article  PubMed  CAS  Google Scholar 

  8. Jones EA, Weissenborn K. Neurology and the liver. J Neurol Neurosurg Psychiatry. 1997;63:279–293.

    Article  PubMed  CAS  Google Scholar 

  9. Albrecht J, Jones EA. Hepatic encephalopathy: molecular mechanisms underlying the clinical syndrome. J Neurol Sci. 1999;170:138–146.

    Article  PubMed  CAS  Google Scholar 

  10. Xiao F, Yu K, Dong F, Liang Y, Jun C, Wei H. The GABAB receptor inhibits activation of hepatic stellate cells. Dig Dis Sci. 2010;55:261–267.

    Article  PubMed  CAS  Google Scholar 

  11. Wang WW, Yang XS, Li X, et al. Changes in the expression of angiotensin II type 1 receptor in the development of liver fibrosis. Chin J Dig Dis. 2004;5:118–122.

    Article  PubMed  CAS  Google Scholar 

  12. Bettler B, Kaupmann K, Mosbacher J, Gassmann M. Molecular structure and physiological functions of GABA(B) receptors. Physiol Rev. 2004;84:835–867.

    Article  PubMed  CAS  Google Scholar 

  13. Castelli MP, Ingianni A, Stefanini E, Gessa GL. Distribution of GABA(B) receptor mRNAs in the rat brain and peripheral organs. Life Sci. 1999;64:1321–1328.

    Article  PubMed  CAS  Google Scholar 

  14. Isomoto S, Kaibara M, Sakurai-Yamashita Y, et al. Cloning and tissue distribution of novel splice variants of the rat GABAB receptor. Biochem Biophys Res Commun. 1998;253:10–15.

    Article  PubMed  CAS  Google Scholar 

  15. Schwarz DA, Barry G, Eliasof SD, Petroski RE, Conlon PJ, Maki RA. Characterization of gamma-aminobutyric acid receptor GABAB(1e), a GABAB(1) splice variant encoding a truncated receptor. J Biol Chem. 2000;275:32174–32181.

    Article  PubMed  CAS  Google Scholar 

  16. Wei K, Eubanks JH, Francis J, Jia Z, Snead OC 3rd. Cloning and tissue distribution of a novel isoform of the rat GABA(B)R1 receptor subunit. NeuroReport. 2001;12:833–837.

    Article  PubMed  CAS  Google Scholar 

  17. Tu H, Xu C, Zhang W, et al. GABAB receptor activation protects neurons from apoptosis via IGF-1 receptor transactivation. J Neurosci. 2010;30:749–759.

    Article  PubMed  CAS  Google Scholar 

  18. Biju MP, Pyroja S, Rajeshkumar NV, Paulose CS. Enhanced GABA(B) receptor in neoplastic rat liver: induction of DNA synthesis by baclofen in hepatocyte cultures. J Biochem Mol Biol Biophys. 2002;6:209–214.

    Article  PubMed  CAS  Google Scholar 

  19. Faroni A, Mantovani C, Shawcross SG, Motta M, Terenghi G, Magnaghi V. Schwann-like adult stem cells derived from bone marrow and adipose tissue express gamma-aminobutyric acid type B receptors. J Neurosci Res. 2011;89:1351–1362.

    Article  PubMed  CAS  Google Scholar 

  20. Velasco I, Tapia R. High extracellular gamma-aminobutyric acid protects cultured neurons against damage induced by the accumulation of endogenous extracellular glutamate. J Neurosci Res. 2002;67:406–410.

    Article  PubMed  CAS  Google Scholar 

  21. Kobuchi S, Tanaka R, Shintani T, et al. Mechanisms underlying the renoprotective effect of {gamma}-aminobutyric acid against the ischemia/reperfusion-induced renal injury in rats. J Pharmacol Exp Ther. 2011;338:767–774.

    Article  PubMed  CAS  Google Scholar 

  22. Zeisberg M, Yang C, Martino M, et al. Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition. J Biol Chem. 2007;282:23337–23347.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The study was supported by the National Natural Science Foundation of China (30800509).

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bingyi Shi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fan, W., Shi, B., Wei, H. et al. γ-Aminobutyric Acid B Receptor Improves Carbon Tetrachloride-Induced Liver Fibrosis in Rats. Dig Dis Sci 58, 1909–1915 (2013). https://doi.org/10.1007/s10620-013-2623-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-013-2623-z

Keywords

Navigation