Effects of 5-hydroxytamine and its antagonists on hepatic stellate cells

Hepatobiliary Pancreat Dis Int. 2006 Feb;5(1):96-100.

Abstract

Background: Hepatic stellate cell (HSC) plays a key role in hepatic fibrosis. This study was undertaken to investigate the expression of 5-hydroxytamine receptors in HSC and the effect of 5-hydroxytamine on biological characteristics of HSC.

Methods: Liver ex vivo perfusion of collagenase and density gradient centrifugation were used to isolate HSCs. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the expression of 5-hydroxytamine receptor subtypes 1A, 2A, 2B and 3. Western blot hybridization was used to elucidate the effect of 5-hydroxytamine and its 2A receptor antagonist ketanserin and 3 receptor antagonist ondanosetron on the expression of transforming growth factor-beta1 (TGF-beta1) and Smad4 in HSC.

Results: HSC expressed 5-hydroxytamine receptor subtypes 1A, 2A and 2B. 5-hydroxytamine significantly increased the expression of TGF-beta1 and Smad4 in HSC (P<0.05). This action can be antagonized by ketanserin, not by ondanosetron.

Conclusions: HSC expresses 5-hydroxytamine receptors. 5-Hydroxytamine could effect the biological characteristics of HSC through its receptor mediation, and may play a role in the pathogenesis of liver cirrhosis and portal hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Gene Expression / drug effects
  • Ketanserin / pharmacology
  • Liver / cytology
  • Liver / drug effects*
  • Liver / metabolism
  • Liver Cirrhosis / etiology
  • Male
  • Ondansetron / pharmacology
  • RNA / genetics
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / biosynthesis
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serotonin / pharmacology*
  • Serotonin Antagonists / pharmacology*
  • Smad4 Protein / biosynthesis
  • Smad4 Protein / drug effects
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / drug effects
  • Transforming Growth Factor beta1

Substances

  • Receptors, Serotonin
  • Serotonin Antagonists
  • Smad4 Protein
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Serotonin
  • Ondansetron
  • RNA
  • Ketanserin